Emodin induces apoptosis in human prostate cancer cell LNCaP

ＷＩＬＥ　ＢＬＡＩＣｌ（ＷＥＬＬ　Ａｓｉａｎ　Ｊ　Ａｎｄｒｏｌ　２００８；１０　ｆ４１：６２５—６３４　ＤＯＩ：１０．１　１　１　１／ｊ．１７４５—７２６２．２００８．００３９７．ｘ　’Ｏｒｉｇｉｎａｌ　Ａｒｔｉｃｌｅ　Ｅｍｏｄｉｎ　ｉｎｄｕｃｅｓ　ａｐｏｐｔｏｓｉｓ　ｎ　ｉｈｕｍａｎ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌ　ＬＮＣａＰ　Ｃｈｕｎ—Ｘｉａｏ　Ｙｕ　。Ｘｉａｏ—Ｑｉａｎ　Ｚｈａｎｇ　，Ｌｕ—Ｄｏｎｇ　Ｋａｎｇ　，Ｐｅｎｇ—Ｊｕ　Ｚｈａｎｇ　，Ｗｅｉ—Ｗｅｎ　Ｃｈｅｎ　，Ｗｅｎ—Ｗｅｎ　Ｌｉｕ　，　Ｑｉｎｇ—Ｗｅｉ　Ｌｉｕ　一．Ｊｉａｎ—Ｙｅ　Ｚｈａｎｇ　’。　Ｄｅｐａｒｔｍｅｎｔ　ｏｆＢｉｏｃｈｅｍｉｓｔｒ．ａｎｄ　ｙＭｏｌｅｃｕｌａｒ　Ｂｉｏｌｏｇｙ，Ｓｈａｎｄｏｎｇ　Ｕｎｉｖｅｒｓｉｔｙ　Ｓｃｈｏｏｌ　ｏｆＭｅｄｉｃｉｎｅ，Ｊｉｎａｎ　２５００１２，Ｃｈｉｎａ　。Ｍｅｒｃｋ　Ｓｈａｒｐ＆Ｄｏｈｍｅ．Ｂｅｉｊｉｎｇ　１００７３８，Ｃｈｉｎａ　ＳＰｏｓｉｔｒｏｎ　Ｅｍｉｓｓｉｏｎ　Ｔｏｍｏｇｒａｐｈｙ　ａｎｄ　Ｃｏｍｐｕｔｅｒ　Ｔｏｍｏｇｒａｐｈｙ（ＰＥＴ－ＣＴ）Ｃｅｎｔｅｒ，Ｓｈａｎｄｏｎｇ　Ｐｒｏｖｉｎｃｉａｌ　Ｈｏｓｐｉｔａｌ，Ｊｉｎａｎ　２５００２１，Ｃｈｉｎａ　Ａｂｓｔｒａｃｔ　Ａｉｍ：Ｔｏ　ｅｌｕｃｉｄａｔｅ　ｅｆｆｅｃｔｓ　ａｎｄ　ｍｅｃｈａｎｉｓｍｓ　ｏｆ　ｅｍｏｄｉｎ　ｉｎ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌｓ．Ｍｅｔｈｏｄｓ：Ｖｉａｂｉｌｉｔｙ　ｏｆ　ｅｍｏｄｉｎ—ｔｒｅａｔｅｄ　ＬＮＣａＰ　ｃｅｌｌｓ　ａｎｄ　ＰＣ一３　ｃｅｌｌｓ　ｗａｓ　ｍｅａｓｕｒｅｄ　ｂｖ　ＭＴｒ　ａｓｓａｙ．Ｆｏｌｌｏｗｉｎｇ　ｅｍｏｄｉｎ　ｔｒｅａｔｍｅｎｔｓ，ＤＮＡ　ｆｒａｇｍｅｎｔａｔｉｏｎ　ｗａｓ　ａｓｓａｙｅｄ　ｂｙ　ａｇａｒｏｓｅ　ｇｅｌ　ｅｌｅｃｔｒｏｐｈｏｒｅｓｉｓ．Ａｐｏｐｔｏｓｉｓ　ｒａｔｅ　ａｎｄ　ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ｏｆ　Ｆａｓ　ａｎｄ　ＦａｓＬ　ｗｅｒｅ　ａｓｓａｙｅｄ　ｂｙ　ｆｌｏｗ　ｃｙｔｏｍｅｔｒｉｃ　ａｎａｌｙｓｉｓ．Ｔｈｅ　ｍＲＮＡ　ｅｘｐｒｅｓｓｉｏｎ　ｌｅｖｅｌｓ　ｏｆ　ａｎｄｒｏｇｅｎ　ｒｅｃｅｐｔｏｒ（ＡＲ），ｐｒｏｓｔａｔｅ—ｓｐｅｃｉｉｆｃ　ａｎｔｉｇｅｎ（ＰＳＡ），ｐ５３，　ｐ２ｌ，Ｂｃｌ一２，Ｂａｘ，ｃａｓｐａｓｅ一３，一８，一９　ａｎｄ　Ｆａｓ　ｗｅｒｅ　ｄｅｔｅｃｔｅｄ　ｂｙ　ＲＴ－ＰＣＲ，ａｎｄ　ｔｈｅ　ｐｒｏｔｅｉｎ　ｅｘｐｒｅｓｓｉｏｎ　ｌｅｖｅｌｓ　ｏｆＡＲ，ｐ５３　ａｎｄ　ｐ２１　ｗｅｒｅ　ｄｅｔｅｃｔｅｄ　ｂＶ　Ｗｌｅｓｔｅｒｎ　ｂｌｏｔ　ａｎａｌｙｓｉｓ．Ｒｅｓｕｌｔｓ：Ｉｎ　ｃｏｎｔｒａｓｔ　ｔｏ　ＰＣ一３，ｅｍｏｄｉｎ　ｃａｕｓｅｄ　ａ　ｍａｒｋｅｄ　ｉｎｃｒｅａｓｅ　ｉｎ　ａｐｏｐｔｏｓｉｓ　ａｎｄ　ａ　ｄｅｃｒｅａｓｅ　ｉｎ　ｃｅｌｌ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ｉｎ　ＬＮＣａＰ　ｃｅｌｌｓ．Ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ｏｆ　ＡＲ　ａｎｄ　ＰＳＡ　ｗａｓ　ｄｅｃｒｅａｓｅｄ　ａｎｄ　ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ｏｆ　ｐ５３　ａｎｄ　Ｄ２　１　ｗａｓ　ｉｎｃｒｅａｓｅｄ　ａｓ　ｔｈｅ　ｅｍｏｄｉｎ　ｃｏｎｃｅｎｔｒａｔｉｏｎｓ　ｗｅｒｅ　ｉｎｃｒｅａｓｅｄ．Ｉｎ　ｔｈｅ　ｓａｍｅ　ｔｉｍｅ，ｅｍｏｄｉｎ　ｉｎｄｕｃｅｄ　ａｐｏｐｔｏｓｉｓ　ｏｆ　ＬＮＣａＰ　ｃｅｌｌｓ　ｔｈｒｏｕｇｈ　ｔｈｅ　ｕｐｒｅｇｕｌａｔｉｏｎ　ｏｆ　ｃａｓｐａｓｅ一３　ａｎｄ一９，ａｓ　ｗｅｌｌ　ａｓ　ｔｈｅ　ｉｎｃｒｅａｓｅ　ｏｆ　Ｂａｘ／Ｂｃｌ一２　ｒａｔｉｏ．Ｈｏｗｅｖｅｒ．ｉｔ　ｄｉｄ　ｎｏｔ　ｉｎｖｏｌｖｅ　ｍｏｄｕｌａｔｉｏｎ　ｏｆ　Ｆａｓ　ｏｒ　ｃａｓｐａｓｅ一８　ｐｒｏｔｅｉｎ　ｅｘｐｒｅｓｓｉｏｎ．Ｃｏｎｃｌｕｓｉｏｎ：Ｉｎ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌｌｉｎｅ，ＬＮＣａＰ，ｅｍｏｄｉｎ　ｉｎｈｉｂｉｔｅｓ　ｔｈｅ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ｂｙ　ＡＲ　ａｎｄ　ｐ５３一ｐ２　１　ｐａｔｈｗａｙｓ，ａｎｄ　ｉｎｄｕｃｅｓ　ａｐｏｐｔｏｓｉｓ　ｖｉａ　ｔｈｅ　ｍｉｔｏｃｈｏｎｄｒｉａ、ｐａｔｈｗａｙ．（Ａｓｉａ１２　ＪＡｎｄｒｏｌ　２ｏｏ８　ＪＭｌ：　ｏ：６２５—６３４｛　Ｋｅｙｗｏｒｄｓ：ｅｍｏｄｉｎ；ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ；ＬＮＣａＰ；ＰＣ一３：ｐｒｏｌｉｆｅｒａｔｉｏｎ；ａｎｄｒｏｇｅｎ　ｒｅｃｅｐｔｏｒ；ｐ５３；ａｐｏｐｔｏｓｉｓ；ｍｉｔｏｃｈｏｎｄｒｉａｌ　ｐａｔｈｗａｙ　１　Ｉｎｔｒｏｄｕｃｔｉｏｎ　Ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｉｓ　ｔｈｅ　ｍｏｓｔ　ｃｏｍｍｏｎ　ｍａｌｉｇｎａｎｔ　ｄｉｓｅａｓｅ　ａｎｄ　ｔｈｅ　ｓｅｃｏｎｄ　ｌｅａｄｉｎｇ　ｃａｕｓｅ　ｏｆ　ｄｅａｔｈ　ｏｆ　ｍａｌｅ　ｃａｎｃｅｒ　ｐａ—　ｔｉｅｎｔｓ　ｉｎ　ｔｈｅ　ＵＳＡ　ａｎｄ　ｉｎ　ｏｔｈｅｒ　ｄｅｖｅｌｏｐｅｄ　ｃｏｕｎｔｒｉｅｓ【１】．　Ｄｅｓｐｉｔｅ　ｔｈａｔ　ｅａｒｌｙ　ｄｅｔｅｃｔｉｏｎ　ａｎｄ　ｄｉａｇｎｏｓｉｓ　ｈａｖｅ　ｂｅｅｎ　ｉｍ—　ｐｒｏｖｅｄ　ｒｅｃｅｎｔｌｙ，ｔｈｅ　ｉｎｃｉｄｅｎｃｅ　ａｎｄ　ｍｏｒｔａｌｉｔｙ　ｒａｔｅｓ　ｏｆ　ｔｈｉｓ　ｃａｎｃｅｒ　ａｒｅ　ｓｔｉｌｌｉｎｃｒｅａｓｉｎｇ　ｓｔｅａｄｉｌｙ．Ｃｕｒｒｅｎｔ　ｐｒｏｓｔａｔｅ　ｃａｎ—　Ｃｏ￣ｅｓｐｏｎｄｅｎｃｅ　ｔｏ：Ｐｒｏｆ．Ｊｉａｎ—Ｙｅ　Ｚｈａｎｇ．Ｄｅｐａｒｔｍｅｎｔ　ｏｆ　Ｂｉｏｃｈｅｍ—　ｉｓｔｒｙ　ａｎｄ　Ｍｏｌｅｃｕｌａｒ　Ｂｉｏｌｏｇｙ．Ｓｈａｎｄｏｎｇ　Ｕｎｉｖｅｒｓｉｔｙ　Ｓｃｈｏｏｌ　ｏｆ　ｃｅｒ　ｔｈｅｒａｐｉｅｓ　ｓｕｃｈ　ａｓ　ｓｕｒｇｅｒｙ，ｃｈｅｍｏｔｈｅｒａｐｙ　ａｎｄ　ｒａｄｉａ—　Ｍｅｄｉｃｉｎｅ，Ｊｉｎａｎ　２５００１　２，Ｃｈｉｎａ．　ｔｉｏｎ　ｔｈｅｒａｐｙ　ａｒｅ　ｏｆ　ｌｉｍｉｔｅｄ　ｅｆｎｃａｃｙ　ａｎｄ　ｒｅｓｕｌｔ　ｉｎ　ｓｉｇｎｉｆｉ—　Ｔｅ１：＋８６—５３　１—８８３８—２０９２　ｃａｎｔ　ｓｉｄｅ—ｅｆｆｅｃｔｓ．Ａｎｄｒｏｇｅｎ　ｒｅｄｕｃｔｉｏｎ　ｔｈｅｒａｐｙ　ｉｓ　ｃｏｍ—　ｍｏｎｌｖ　ｕｓｅｄ　ｔｏ　ｃｏｎｔｒｏｌ　ｈｏｒｍｏｎｅ—ｓｅｎｓｉｔｉｖｅ　ｔｕｍｏｒ　ｃｅｌｌｓ；　ｈｏｗｅｖｅｒ，ａｂｌａｔｉｏｎ　ｒｅｓｉｓｔａｎｔ　ｃｌｏｎｅｓ　ｏｆｔｅｎ　ｅｍｅｒｇｅ　ａｆｔｅｒ　Ｅ．ｍａｉ１：ｚｈｊｙ＠ｓｄｕ．ｅｄｕ．ｃａ　Ｄｒ　Ｑｉｎｇ—Ｗｅｉ　Ｌｉｕ　Ｐｏｓｉｔｒｏｎ　Ｅｍｉｓｓｉｏｎ　Ｔｏｍｏｇｒａｐｈｙ　ａｎｄ　Ｃｏｍｐｕｔｅｒ　Ｔｏｍｏｇｒａｐｈｙ（ＰＥＴ－ＣＴ）Ｃｅｎｔｅｒ，Ｓｈａｎｄｏｎｇ　Ｐｒｏｖｉｎｃｉａｌ　Ｈｏｓｐｉｔｌ，Ｊｉｎａｎ　ａ２５００２１，Ｃｈｉｎａ．　ｈｅｒｔａｐｙ『２１．Ａｂｌａｔｉｏｎ—ｒｅｓｉｓｔａｎｔ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｉｓ　ａｌｍｏｓｔ　ｉｎｃｕｒａｂｌｅ『３１．Ｔｈｅｒｅｆｏｒｅ，ｎｏｖｅｌ　ｅｆｆｅｃｔｉｖｅ　ｔｈｅｒａｐｉｅｓ，ｉｎ—　ｃｌｕｄｉｎｇ　ｂｉｏｔｈｅｒａｐｙ，ａｒｅ　ｕｒｇｅｎｔｌｙ　ｎｅｅｄｅｄ　ｔｏ　ｂｅ　ｄｅｖｅｌｏｐｅｄ．　Ｔｅｌ：＋８６—５３１—８７０６—０３１６　Ｅ　ｍａｉｌ：ｌｉｕｑｉｎｇｗｅｉ６＠ｙａｈｏｏ．ｃｏｒｎ．ｃｎ　Ｒｅｃｅｉｖｅｄ　２００７—０５—２３　Ａｃｃｅｐｔｅｄ　２００８—０１一ｌ１　Ｉｎ　ｔｈｅ　ｓｅａｒｃｈ　ｆｏｒ　ａｌｔｅｒｎａｔｉｖｅ　ａｎｄ　ｐｒｅｖｅｎｔｉｖｅ　ｔｈｅｒａｐｉｅｓ　⑥２００８．Ａｓｉａｎ　Ｊｏｕｒｎａｌ　ｏｆ　Ａｎｄｒｏｌｏｇｙ，ＳＩＭＭ　ａｎｄ　ＳＪＴＵ．Ａｌｌ　ｒｉｇｈｔｓ　ｒｅｓｅｒｖｅｄ　６２５　维普资讯 http://www.cqvip.com

Ｅｍｏｄｉｎ　ｉｎｄｕｃｅｓ　ａｐｏｐｔｏｓｉｓ　ｉｎ　ＬＮＣａＰ　ｃｅｌｌ　ｆｏｒ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ，ａｔｔｅｎｔｉｏｎ　ｈａｓ　ｂｅｅｎ　ｆｏｃｕｓｅｄ　ｏｎ　ｐｌａｎｔｓ．　Ｍａｎｙ　ｐｈｙｔｏｃｈｅｍｉｃａｌｓ　ｓｕｃｈ　ａｓ　ｇｅｎｉｓｔｅｉｎ　ａｎｄ　ｃｕｒｃｕｍｉｎ　ｈａｖｅ　ｂｅｅｎ　ｓｈｏｗｎ　ｔｏ　ｐｏｓｓｅｓｓ　ｓｕｂｓｔａｎｔｉａｌ　ａｎｔｉｃａｎｃｅｒ　ａｃ．　ｔｉｖｉｔｉｅｓ　ｉｎ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ，ａｎｄ　ｃｌｉｎｉｃａｌ　ｔｒｉａｌｓ　ｕｓｉｎｇ　ｔｈｅｓｅ　ｐｈｙｔｏｃｈｅｍｉｃａｌｓ　ｔｏ　ｐｒｅｖｅｎｔ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ａｒｅ　ｏｎｇｏｉｎｇ　［４，５］．Ｅｍｏｄｉｎ（１，２，８－ｔｒｉｈｙｄｒｏｘｙ－６－ｍｅｔｈｙｌａｎｔｈｒａｑｕｉｎｏｎｅ），　ａｌｌ　ａｃｔｉｖｅ　ｃｏｍｐｏｎｅｎｔ　ｃｏｎｔａｉｎｅｄ　ｉｎ　ｔｈｅ　ｒｏｏｔ　ｎａｄ　ｒｈｉｚｏｍｅ　ｏｆ　Ｒｈｅｕｍ　ｐａｌｍａｔｕｍ　Ｌ（Ｐｏｌｙｇｏｎａｃｅａｅ）［６，７］，ｈａｓ　ｒｅｃｅｉｖｅｄ　ａ　ｇｒｅａｔ　ｄｅａｌ　ｏｆ　ａｔｔｅｎｔｉｏｎ　ｒｅｃｅｎｔｌｙ．Ｓｅｖｅｒａｌ　ｒｅｃｅｎｔ　ｏｂｓｅｒｖａ．　ｔｉｏｎｓ　ｈａｖｅ　ｓｈｏｗｎ　ｔｈａｔ　ｅｍｏｄｉｎ　ｈａｓ　ａｎｔｉ．ｔｕｍｏｒ，ａｎｔｉｂａｃｔｅｒｉａｌ，　ｄｉｕｒｅｔｉｃ　ｎａｄ　ｖａｓｏｒｅｌａｘａｎｔ　ｅｆｆｅｃｔｓ『８—１０１．Ａｌｔｈｏｕｇｈ　ｉｔ　ｈａｓ　ｂｅｅｎ　ｃｌａｉｍｅｄ　ｔｏ　ｈａｖｅ　ＤＯｔｅｎｔ　ａｎｔｉｃａｎｃｅｒ　ａｃｔｉｖｉｔｙ　ｉｎ　ｔｈｅ　ｃａｓｅ　ｏｆ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ［１ｌ】，ｔｈｅ　ｍｏｌｅｃｕｌｒａ　ｍｅｃｈａｎｉｓｍｓ　ｏｆ　ｅｍｏ．　ｄｉｎ　ｔｈａｔ　ｐｒｏｄｕｃｅ　ｉｔｓ　ｂｉｏｌｏｇｉｃａｌ　ｅｆｆｅｃｔｓ　ｉｎ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌｓ　ｈａｖｅ　ｎｏｔ　ｂｅｅｎ　ｗｅｌ１．ｃｈａｒａｃｔｅｒｉｚｅｄ．　Ｉｎ　ｔｈｅ　ｎｏｒｍａｌ　ｐｒｏｓｔａｔｅ，ａｎｄｒｏｇｅｎｓ　ｐｌａｙ　ａ　ｃｒｉｔｉｃａｌ　ｒｏｌｅ　ｉｎ　ｒｅｇｕｌａｔｉｎｇ　ｔｈｅ　ｇｒｏｗｔｈ，ｄｉｆｆｅｒｅｎｔｉａｔｉｏｎ　ａｎｄ　ｓｕｒｖｉｖａｌ　ｏｆ　ｅｐｉｈｔｅｌｉｌａ　ｃｅｌｌｓ［１　２］．Ｅｖｉｄｅｎｃｅ　ｓｈｏｗｓ　ｔｈａｔ　ｎａｄｒｏｇｅｎｓ　ｒａｅ　ａｌｓｏ　ｉｎｖｏｌｖｅｄ　ｎｉ　ｔｈｅ　ｄｅｖｅｌｏｐｍｅｎｔ　ｎａｄ　ｐｒｏｇｒｅｓｓｉｏｎ　ｏｆ　ｐｒｏｓ．　ｔａｔｅ　ｃａｎｃｅｒ．Ｔｈｅ　ｂｉｏｌｏｇｉｃａｌ　ｅｆｆｅｃｔｓ　ｏｆ　ａｎｄｒｏｇｅｎｓ　ｉｎ　ｔｈｅ　ｐｒｏｓｔａｔｅ　ｒａｅ　ｍｅｄｉａｔｅｄ　ｂｙ　ｔｈｅ　ａｎｄｒｏｇｅｎ　ｒｅｃｅｐｔｏｒ（ＡＲ），ａ　ｌｉｇａｎｄ．．ａｃｔｉｖａｔｅｄ　ｔｒａｎｓｃｒｉｐｔｉｏｎ　ｆａｃｔｏｒ　ｏｆ　ｔｈｅ　ｎｕｃｌｅａｒ　ｒｅ．．　ｃｅｐｔｏｒ　ｓｕｐｅｒｆａｍｉｌｙ［１　３］．Ｔｈｅｒｅｆｏｒｅ，ｔｈｅ　ＡＲ　ｈａｓ　ａ　ｃｒｉｔｉ．　ｃａｌ　ｒｏｌｅ　ｉｎ　ｔｈｅ　ｄｅｖｅｌｏｐｍｅｎｔ　ｏｆ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ．　Ｐ５３　ｐｒｏｔｅｉｎ　ｉｓ　ａ　ｔｒａｎｓｃｒｉｐｔｉｏｎ　ｆａｃｔｏｒ　ａｎｄ　ｒｅｇｕｌａｔｅｓ　ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ｏｆ　ｓｅｖｅｒａｌ　ｇｒｏｗｔｈ　ｃｏｎｔｒｏｌ　ｇｅｎｅｓ　ｉｎｖｏｌｖｅｄ　ｉｎ　ｃｅｌｌ　ｃｙｃｌｅ　ｐｒｏｇｒｅｓｓｉｏｎ，ＤＮＡ　ｒｅｐａｉｒ，ａｐｏｐｔｏｓｉｓ　ｎａｄ　ａｎｇｉｏｇｅｎｅｓｉｓ　『ｌ４＿１６］．Ｉｔｉｓ　ａｍａｊｏｒｔｕｍｏｒ　ｓｕｐｐｒｅｓｓｏｒｔｈａｔｃａｎｌｅａｄｔｏｔｈｅ　ｎｉｄｕｃｔｉｏｎ　ｏｆａ　ｄｏｗｎｓｔｒｅａｍ　ｔａｒｇｅｔ　ｇｅｎｅ　ｐ２　ｗ鲫，（ｉｐ１　ｔｏ　ｉｎｈｉｂｉｔ　ｈｔｅｃｅｌｌ　ｃｙｃｌｅｓａｎｄｃａｕｓｅｃｅｌｌｇｒｏｗｔｈ　ａｒｒｅｓｔ，ａｎｄｉｔｉｓｔｈｅｋｅｖ　ｉｎ　ｔｈｅ　ｃｅｌｌｕｌａｒ　ａｎｄ　ｍｏｌｅｃｕｌａｒ　ｓｉｇｎａｌｉｎｇ　ｃａｓｃａｄｅｓ　ｔｈａｔ　ｇｕｉｄｅ　ｌｅｔｈａｌ　ＤＮＡ　ｄａｍａｇｅ　ｎｉ　ｃｅｌｌｓ　ｔｏ　ｓｅｌｆ－ｄｅｓｔｒｕｃｔｉｏｎ．　Ａｐｏｐｔｏｓｉｓｉｓ　ａｍａｊｏｒｆｏｒｍｏｆｃｅｌｌｄｅａｔｈａｎｄａｎｉｍｐｏｒ．　ｔｎａｔ　ｐｒｏｃｅｓｓ　ｆｏｒ　ｎｏｒｍａｌ　ｄｅｖｅｌｏｐｍｅｎｔ　ａｎｄ　ｓｕｐｐｒｅｓｓｉｏｎ　ｏｆ　ｏｎｃｏｇｅｎｅｓｉｓ．Ｉｔ　ｉｓ　ｃｈａｒａｃｔｅｒｉｚｅｄ　ｂｙ　ａ　ｓｅｒｉｅｓ　ｏｆ　ｓｔｅｒｅｏｔｙｐｉｃ　ｍｏｌｅｃｕｌａｒ　ｆｅａｔｕｒｅｓ，ｓｕｃｈ　ａｓ　ａｃｔｉｖａｔｉｏｎ　ｏｆ　ｃａｓｐａｓｅｓ　ａｎｄ　ｅｘｐｒｅｓｓｉｏｎ　ａｎｄ　ｔｒａｎｓｌｏｃａｔｉｏｎ　ｏｆ　Ｂｃ１．２　ｆａｍｉｌｙ　ｐｒｏｔｅｉｎｓ．　Ｃａｓｐａｓｅｓ，ａ　ｆａｍｉｌｙ　ｏｆ　ｃｙｓｔｅｉｎｅ　ｐｒｏｔｅａｓｅｓ，ｐｌａｙ　ａ　ｃｒｉｔｉｃａｌ　ｒｏｌｅｄｕｒｉｎｇａｐｏｐｔｏｓｉｓ．Ｔｈｅｒｅａｒｅａｔｌｅａｓｔｔｗｏｍａｊｏｒｍｅｃｈａ．　ｎｉｓｍｓ　ｂｙ　ｗｈｉｃｈ　ａ　ｃａｓｐａｓｅ　ｃａｓｃａｄｅ　ｒｅｓｕｌｔｓ　ｉｎ　ｔｈｅ　ａｃｔｉｖａ．　ｔｉｏｎ　ｏｆ　ｅｆｆｅｃｔｏｒ　ｃａｓｐａｓｅｓ（ｃａｓｐａｓｅ．３，．６　ａｎｄ．７），ｏｎｅ　ｉｎ．　ｖｏｌｖｉｎｇ　ｃａｓｐａｓｅ－８　ａｎｄ　ｈｔｅ　ｏｔｈｅｒ　ｉｎｖｏｌｖｉｎｇ　ｃａｓｐａｓｅ－９［１　７］．　Ｔｈｅｒｅｆｏｒｅ，ｔｗｏｔｙｐｉｃａｌ　ａｐｏｐｔｏｓｉｓｐａｔｈｗａｙｓ，ｒｅｃｅｐｔｏｒ（Ｆａｓ）－　ｍｅｄｉａｔｅｄ（ｉｎｖｏｌｖｉｎｇ　ｃａｓｐａｓｅ－８，ｄｅａｔｈ－ｎｉｄｕｃｉｎｇ　ｓｉｇｎａ１）ａｎｄ　ｃｈｅｍｉｃａ１．ｉｎｄｕｃｅｄ（ｉｎｖｏｌｖｉｎｇ　ｃａｓｐａｓｅ．９，ｍｉｔｏｃｈｏｎｄｒｉａｌ　ｐａｔｈｗａｙ）ａｐｏｐｔｏｓｉｓ，ｈａｖｅ　ｂｅｅｎ　ｓｕｇｇｅｓｔｅｄ［１　８］．Ｍｏｒｅｏｖｅｒ，　ｈｔｅ　Ｂｃ１．２　ｆａｍｉｌｙ　ｐｒｏｔｅｉｎｓ．ｓｕｃｈ　ａｓ　Ｂｃ１．２　ａｎｄ　Ｂａｘ，ａｒｅ　ｔｈｅ　ｂｅｓｔ－ｃｈａｒａｃｔｅｒｉｚｅｄ　ｒｅｇｕｌａｔｏｒｓ　ｏｆ　ａｐｏｐｔｏｓｉｓ［１　９］．Ｍａｎｙ　・６２６・　ｒｅｐｏｒｔｓ　ｈａｖｅ　ｉｎｄｉｃａｔｅｄ　ｔｈａｔ　ａｃｔｉｖａｔｉｏｎ　ｏｆ　ｃａｓｐａｓｅ．３　ｉｓ　ｂｌｏｃｋｅｄ　ｂｙ　ａｎｔｉ．ａｐｏｐｔｏｓｉｓ　ｍｅｍｂｅｒｓ　ｏｆ　ｔｈｅ　Ｂｃ１．２　ｆａｍｉｌｙ，　ｓｕｃｈ　ａｓ　Ｂｃｌ－２，ａｎｄ　ｐｒｏｍｏｔｅｄ　ｂｙ　ｐｒｏａｐｏｐｔｏｔｉｃ　ｍｅｍｂｅｒｓ，　ｓｕｃｈ　ａｓ　Ｂａｘ『２０，２１１．　ｈＴｅ　ｍａｊｏｒ　ｐｕｒｐｏｓｅ　ｏｆ　ｔｈｅ　ｐｒｅｓｅｎｔ　ｓｔｕｄｙ　ｉｓ　ｔｏ　ｉｎｖｅｓｔｉ．　ｇａｔｅ　ｔｈｅ　ｅｆｆｅｃｔｓ　ｏｆ　ｅｍｏｄｉｎ　ｏｎ　ｔｈｅ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ａｎｄ　ａｐｏｐｔｏｓｉｓ　ｏｆ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌ　ｌｉｎｅ　ＬＮＣａＰ　ａｎｄ　ｔｏ　ｄｉｓ．　ｃｏｖｅｒ　ａ　ｐｏｓｓｉｂｌｅ　ｍｅｃｈａｎｉｓｍ　ｉｎｖｏｌｖｅｄ　ｉｎ　ｅｍｏｄｉｎ　ａｃｔｉｏｎｓ　ｉｎ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌｓ．　２　Ｍａｔｅｒｉａｌｓ　ａｎｄ　ｍｅｔｈｏｄｓ　２．１　ＣｅＩＩ　ｃｕｌｔｕｒｅｓ　ａｎｄ　ｔｒｅａｔｍｅｎ￣　ｌｅｈｕｍａｎｐｒｏｓｔａｔｅ　ｃａｎｃｅｒｃｅｌｌｌｉｎｅｓＬＮＣａＰａｎｄＰＣ．３　ｗｅｒｅｏｂｔａｉｎｅｄｆｒｏｍｔｈｅＡｍｅｒｉｃａｎＴｙｐｅＣｕｌｔｕｒｅＣｏｌｌｃｅｔｉｏｎ　（Ｍａｎａｓｓａｓ，ＶＡ，ＵＳＡ）．ＬＮＣａＰ　ｃｅｌｌ　ｌｉｎｅ　ｗａｓ　ｅｓｔａｂｌｉｓｈｅｄ　ｒｆｏｍ　ａ　ｌｙｍｐｈ　ｎｏｄｅ　ｍｅｔａｓｔａｓｉｓ　ｏｆ　ａ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｐａｔｉｅｎｔ　ａｎｄ　ｅｘｐｒｅｓｓｅｄ　ｍｕｔａｎｔ．ｂｕｔ　ｆｕｎｃｔｉｏｎａｌ　ＡＲ　ａｎｄ　ａ　ｎｕｍｂｅｒ　ｏｆ　ａｎｄｒｏｇｅｎ’ｉｎｄｕｃｉｂｌｅ　ｇｅｎｅｓ（ｅ．ｇ．ｐｒｏｓｔａｔｅ　ｓｐｅｃｉｆｉｃ　ａｎｔｉｇｅｎ　［ＰＳＡ］）．ＬＮＣａＰ　ａｎｄ　ＰＣ．３　ｃｅｌｌｓ　ｗｅｒｅ　ｓｅｅｄｅｄ　ｉｎ　３５．ＩｎｌＴｌ　ｃｕｌｔｕｒｅ　ｄｉｓｈｅｓ　ｉｎ　ＲＰＭＩ　ｌ　６４０　ｍｅｄｉｕｍ（Ｇｉｂｃｏ　ＢＲＬ　Ｇａｉｔｈｅｒｓｂｕｒｇ，ＭＤ，ＵＳＡ）ｓｕｐｐｌｅｍｅｎｔｅｄ　ｗｉｔｈ　１　０％ｆｅｔａｌ　ｂｏｖｉｎｅ　ｓｅｒｕｍ（ＦＢＳ）ａｎｄ　５％ＣＯ２　ａｔ　３７ｏＣ　ｕｎｔｉｌ　ｒｅａｃｈｉｎｇ　ａｐｐｒｏｘｉｍａｔｅｌｙ　５０％－７０％ｃｏｎｆｌｕｅｎｃｅ．Ｔｈｅ　ｃｅｌｌｓ　ｗｅｒｅ　ｍａｉｎｔａｉｎｅｄ　ｉｎ　ｓｅｒｕｍ．ｆｒｅｅ　ＲＰＭＩ　１　６４０　ｍｅｄｉｕｍ　ｆｏｒ　ａ　ｆｕｒ．　ｔｈｅｒ　２４　ｈ　ａｎｄ　ｔｈｅｎ　ｔｒｅａｔｅｄ　ｗｉｔｈ　ｅｍｏｄｉｎ　ａｔ　ｉｎｄｉｃａｔｅｄ　ｃｏｎ．　ｃｅｎｔｒａｔｉｏｎｓ　ｉｎ　ＲＰＭＩ　ｌ　６４０　ｍｅｄｉｕｍ　ｃｏｎｔａｉｎｉｎｇ　５％ＦＢＳ．　Ｅｍｏｄｉｎ（ａｔ　９０％ｐｕｒｉｔｙ　ｂｖ　ＨＰＬＣ：Ｎｏ．４５　ｌ７０；Ｓｉｇｍａ　Ｃｈｅｍｉｃａｌ　Ｃｏｍｐａｎｙ，Ｓｔ．Ｌｏｕｉｓ，ＭＯ，ＵＳＡ）ｗａｓ　ｄｉｓｓｏｌｖｅｄ　ｉｎ　ｄｉｍｅｔｈｙｌ　ｓｕｌｆｏｘｉｄｅ（ＤＭＳ０）．ｗｈｉｃｈ　ｌａｓｏ　ｗａｓ　ｕｓｅｄ　ａｓ　ａ　ｃｏｎｔｒｏｌ　ｖｅｈｉｃｌｅ　ｉｎ　ｔｈｅ　ｃｅｌｌ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ａｓｓａｙ　ａｎｄ　ｉｎ　ｏｔｈｅｒ　ａｎａｌＶｓｅｓ／ａｓｓａＶｓ　ｆｏｒ　ｔｈｅ　ｐｒｅｓｅｎｔ　ｓｔｕｄｙ．Ｉｎ　ｔｈｅｓｅ　ａｓｓａｙｓ，　ｅｖｅｒｙ　ｇｒｏｕｐ　ｒｅｃｅｉｖｅｄ　ｓａ！Ｔｌｅ　ａｍｏｕｎｔ　ｏｆ　ＤＭＳ０．　２．２　Ｃｅｌｌ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ａｓｓａｙ　Ｔｈｅ　ｅｆｆｅｃｔ　ｏｆ　ｅｍｏｄｉｎ　ｏｎ　ｃｅｌｌ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ｗａｓ　ｍｅａ．　ｓｕｒｅｄ　ｂｙ　３－（４，５－ｄｉｍｅｔｈｙｌｔｈｉａｚｏｌ－２－ｙ１）－２，５－ｄｉｐｈｅｎｙｌｔｅ—　ｔｒａｚｏｌｉｕｍ　ｂｒｏｍｉｄｅ（ＭＴＴ）ａｓｓａｙ．Ｃｅｌｌｓ　ｗｅｒｅ　ｃｕｌｔｕｒｅｄ　ｉｎ　９６．ｗｅｌｌ　ｐｌａｔｅｓ　ａｔ　ａ　ｄｅｎｓｉｔｙ　ｏｆ　ｌ　０００　ｃｅｌｌｓ／ｗｅｌｌ　ｗｉｍ　ｌ００　ｕＬ　ｏｆ　ｃｕｌｔｕｒｅ　ｍｅｄｉｕｍ．Ａｆｔｅｒ　２　ｄａｙｓ　ｉｎｃｕｂａｔｉｏｎ．ｃｅｌｌｓ　ｗｅｒｅ　ｔｒｅａｔｅｄ　ｗｉｔｈ　ｄｉｆｆｅｒｅｎｔ　ｃｏｎｃｅｎｔｒａｔｉｏｎｓ　ｏｆ　ｅｍｏｄｉｎ（１　０，２０，　３０　ａｎｄ　４０　Ｉ￣ｍｏｌ／Ｌ）ａｎｄ　ＤＭＳＯ（ｆｉｎａｌ　ｃｏｎｃｅｎｔｒａｔｉｏｎ．　０．０ｌ％１　ａｓ　ｔｈｅ　ｃｏｎｔｒｏｌ　ａｎｄ　ｔｈｅｎ　ｉｎｃｕｂａｔｅｄ　ｆｏｒ　ａｎ　ａｄｄｉ．　ｔｉｏｎａｌ　２４，４８　Ｏｒ　７２　ｈ．Ａｔ　ｔｈｅ　ｔｉｍｅ　ｏｆ　ｅｖａｌｕａｔｉｏｎ　ｏｆ　ｃｅｌｌ　ｒｇｏｗｔｈ，１０　Ｍ１Ｔｒ（ｆｉｎａｌ　ｃｏｎｃｅｎｔｒａｔｉｏｎ，５　ｇ／Ｌ）ｗａｓａｄｄｅｄ　ｉｎｔｏ　ｅａｃｈ　ｗｅｌ１．Ａｆｔｅｒ　４．ｈ　ｉｎｃｕｂａｔｉｏｎ．ｆｏｒｍａｚａｎ　ｃｒｙｓｔａｌｓ　ｐｒｏｄｕｃｅｄｂｙｒｉｖｉｎｇｃｕｌｔｕｒｅｄｃｅｌｌｓｗｅｒｅｄｉｓｓｏｌｖｅｄｗｉｔｈ　ｌ００　ｕＬ　ＤＭＳＯ　ａｎｄ　ｍｅａｓｕｒｅｄ　ｕｓｉｎｇ　ａ　ｐｌａｔｅ　ｍｉｃｒｏｒｅａｄｅｒ（Ｔｅｃａｎ　，，ｆｔｐ：／／ｗｗｗ．ａｓｉａａｎｄｒｏ．ｃｏｒｎ；ａｊａ＠ｓｉｂｓ．８ｃ．ｃｎ　维普资讯 http://www.cqvip.com

Ａｓｉａｎ　Ｊ　Ａｎｄｒｏｌ　２００８；１０　ｆ４）：６２５—６３４　Ｓｐｅｃｔｒａ，Ｗｅｔｚｌａｒ，Ｇｅｒｍａｎｙ）ａｔ　ａ　ｗａｖｅｌｅｎｇｔｈ　ｏｆ　５７０　ｎｍ．　Ｔｈｅ　ｐｅｒｃｅｎｔａｇｅ　ｏｆ　ｃｅｌｌ　ｖｉａｂｉｌｉｔｙ　ｗａｓ　ｃａｌｃｕｌａｔｅｄ　ａｓ　ｆｏｌｌｏｗｓ：　１．５％ａｇａｒｏｓｅ　ｇｅ１．ｓｔａｉｎｅｄ　ｗｉｔｈ　ｅｔｈｉｄｉｕｍ　ｂｒｏｍｉｄｅ，ａｎｄ　ｔｈｅｎ　ｐｈｏｔｏｇｒａｐｈｅｄ　ｕｎｄｅｒ　ＵＶ　ｌｉｇｈｔ．｛］－ａｃｔｉｎ　ｗａｓ　ｕｓｅｄ　ｔｏ　ｎｏｒｍａｌｉｚｅ　ｔｈｅ　ｑｕａｎｔｉｔｙ　ｏｆ　ｃＤＮＡ．　Ｃｅｌｌ　ｖｉａｂｉｌｉｔｙ（％）＝Ａ５７ｏ（ｄｒｕｇ）／Ａ５７ｏ（ｃｏｎｔｒｏ１）ｘ　１００　２．３　０ｂｓｅｒｖａｔｉｏｎ　ｏｆｍｏｒｐｈｏｌｏｇｉｃ　ｃｈａｎｇｅｓ　ＬＮＣａＰ　ａｎｄ　ＰＣ．３　ｃｅｌｌｓ　ｉｎ　ＲＰＭＩ．１６４０　ｃｏｎｔａｉｎｉｎｇ　１０％　２　７　ｓＤＳ－ｐｏｌｙａｃｒｙｌａｍｉｄｅ　ｇｅｌ　ｅｌｅｃｔｒｏｐｈｏｒｅｓｉｓ　ａｎｄ　Ｗｅｓｔｅｒｎ　ｂｌｏｔ　ａｎａｌｙｓｉｓ　ＬＮＣａＰ　ｃｅｌｌｓ　ｗｅｒｅ　ｔｒｅａｔｅｄ　ｗｉｔｈ　ｅｍｏｄｉｎ　ｆｏｒ　ｄｉｆｆｅｒｅｎｔ　ｄｏｓｅｓ　ａｎｄ　ｔｉｍｅｓ．Ｂｏｔｈ　ａｄｈｅｒｅｎｔ　ａｎｄ　ｆｌｏａｔｉｎｇ　ｃｅｌｌｓ　ｗｅｒｅ　ＦＢＳ　ｗｅｒｅ　ｓｅｅｄｅｄ　ｉｎｔｏ　６．ｗｅｌｌ　ｃｕｌｔｕｒｅ　ｐｌａｔｅｓ　ａｎｄ　ｃｕｌｔｕｒｅｄ　ｆｏｒ　４８　ｈ　ｂｅｆｏｒｅ　ｔｈｅ　ｔｒｅａｔｍｅｎｔ　ｗｉｔｈ　ｄｉｆｆｅｒｅｎｔ　ｃｏｎｃｅｎｔｒａ．　ｔｉｏｎｓ　ｏｆ　ｅｍｏｄｉｎ（１　０，２０，３０　ａｎｄ　４０　ｌａｍｏｌ／Ｌ）ａｎｄ　ＤＭＳＯ　ｆｆｉｎａｌ　ｃｏｎｃｅｎｔｒａｔｉｏｎ．０．０ｌ％）ａｓ　ｔｈｅ　ｃｏｎｔｒｏ１．Ｔｈｅ　ｃｅｌｌｕｌａｒ　ｍｏｒｐｈｏｌｏｇｙ　ｗａｓ　ｏｂｓｅｒｖｅｄ　ｕｓｉｎｇ　ａ　ｐｈａｓｅ－－ｃｏｎｔｒａｓｔ　ｍｉ－－　ｃｒｏｓｃｏｐｙ　４８　ｈ　ａｆｔｅｒ　ｅｍｏｄｉｎ　ｔｒｅａｔｍｅｎｔｓ．　ｈａｒｖｅｓｔｅｄ　ａｎｄ　ｌｙｓｅｄ　ｗｉｔｈ　ｃｅｌｌ　１ｙｓｅｓ　ｂｕｆｆｅｒ（５Ｏ　ｍｍｏｌ／Ｌ　Ｔｒｉｓ・Ｈｅ１，ｐＨ　８．０，１５０　ｍｍｏｌ／Ｌ　ＮａＣ１，０．１％ＳＤＳ，１００　ｎＬ　ｏｆ　ＰＭＳＦ，１　ｐｇ／ｍＬ　ｏｆ　ａｐｒｏｔｉｎｉｎ，ａｎｄ　１％ＮＰ一４０）．Ｃｅｌｌ　ｅｘｔｒａｃｔｓ　ｗｅｒｅ　ｑｕａｎｔｉｉｅｄ　ａｃｃｏｒｄｉｆｎｇ　ｔｏ　ｔｈｅ　ＢＣＡ　ｍｅｔｈｏｄ．　Ｆｏｒ　Ｗｅｓｔｅｒｎ　ｂｌｏｔ　ａｎａｌｙｓｉｓ，４０　ＬＬ２　ｏｆ　ｐｒｏｔｅｉｎ　ｅｘｔｒａｃｔ　ｗａｓ　２．４　Ｆ１ｏｗ　ｃｙｔｏｍｅｔｒｉｃ　ａｎａｌｙｓｉｓ　ＬＮＣａＰ　ｃｅｌｌｓ．ｂｏｔｈ　ａｄｈｅｒｅｎｔ　ｎｄ　ａｌｏａｔｉｆｎｇ．ｗｅｒｅ　ｐｅｌｌｅｔｅｄ　ａｎｄ　ｗａｓｈｅｄ　ｗｉｔｈ　ＰＢＳ．Ｔｈｅ　ｃｅｌｌｓ　ｗｅｒｅ　ｆｉｘｅｄ　ｉｎ　７５％　ｅｔｈａｎｏｌ　ａｔ　４。Ｃ　ｏｖｅｒｎｉｇｈｔ．Ｓａｍｐｌｅｓ　ｗｅｒｅ　ａｎａｌｙｚｅｄ　ｕｓｉｎｇ　ａ　ｓｅｐａｒａｔｅｄ　ｂｙ　ｅ１ｅｃｔｒｏｐｈｏｒｅｓｉｓ　ｏｎ　１０％ＳＤＳ、ＰＡＧＥ，ａｎｄ　ｅ１ｅｃｔｒｏｂ１ｏｔｔｅｄ　ｏｎｔｏ　ｎｉｔｒｏｃｅ１１ｕ１ｏｓｅ　ｍｅｍｂｒａｎｅ．　Ａｆｔｅｒ　ｂｌｏｃｋｉｎｇ　ａｎｄ　ｗａｓｈｉｎｇ，ｔｈｅ　ｍｅｍｂｒａｎｅ　ｗａｓ　ｉｎｃｕｂａｔｅｄ　ｌｏｗ　ｃｙｔｏｍｅｔｆｅｒ（Ｂｅｃｔｏｎ　Ｄｉｃｋｉｎｓｏｎ　ＦＡＣＳｃａｎ．Ｆｒａｎｋｌｉｎ　Ｌａｋｅｓ，ＣＡ，ＵＳＡ）．Ｐｒｏｐｉｄｉｕｍ　ｉｏｄｉｄｅ（ＰＩ）ｓｔａｉｎｉｎｇ　ｗａｓ　ｕｓｅｄ　ｔｏ　ｄｅｔｅｒｍｉｎｅ　ｔｈｅ　ｐｅｒｃｅｎｔａｇｅ　ｏｆ　ｃｅｌｌｓ　ｉｎ　ｄｉｆｆｅｒｅｎｔ　ｐｈａｓｅｓ　ｏｆ　ｔｈｅ　ｃｅｌ１　ｃｙｃｌｅ，ａｎｄ　ｓｕｂ．Ｇｌ　ｐｅａｋｓ　ｗｅｒｅ　ｐｒｅ．　ｓｅｎｔｅｄ　ａｎｄ　ｕｓｅｄ　ｔｏ　ｃａｌｃｕｌａｔｅ　ｔｈｅ　ａｐｏｐｔｏｓｉｓ　ｏｆ　ｔｈｅ　ｃｅｌｌｓ．　Ｆｌｕｏｒｅｓｃｅｎｔ　ｌａｂｅｌｉｎｇ　ｍｏｎｏｃｌｏｎａｌ　ａｎｔｉｂｏｄｙ　ｗａｓ　ｕｓｅｄ　ｔｏ　ｗｉｔｈ　ｈｕｍａｎ　ｓｐｅｃｉｉｆｃ　ｎｔａｉ．ＡＲ。ａｎｔｉ．ｐ５３　ｆＢＤ　Ｂｉｏｓｃｉｅｎｃｅｓ）　ａｎｄ　ａｎｔｉ—ｐ２１　ｐ　ａｎｔｉｂｏｄｉｅｓ（Ｃｅｌｌ　Ｓｉｇｎａｌｌｉｎｇ，Ｂｅｖｅｒｌｙ，　ＭＡ．ＵＳＡ）ａｔ　４。Ｃ　ｆｏｒ　１　２　ｈ，ｆｏｌｌｏｗｅｄ　ｂｙ　ｔｈｅ　ｉｎｃｕｂａｔｉｏｎ　ｗｉｔｈ　ｐｅｒｏｘｉｄａｓｅ．１ａｂｅｌｅｄ　ｓｅｃｏｎｄ　ａｎｔｉｂｏｄｙ　ｆｏｒ　１　ｈ　ａｔ　ｒｏｏｍ　ｔｅｍｐｅｒａｔｕｒｅ．Ｉｍｍｕｎｏｒｅａｃｔｉｖｅ　ｂａｎｄｓ　ｗｅｒｅ　ｖｉ—　ｓｕａｌｉｚｅｄ　ｕｓｉｎｇ　ｅｎｈａｎｃｅｄ　ｃｈｅｍｉｌｕｍｉｎｅｓｃｅｎｃｅ（Ｓａｎｔａ　Ｃｒｕｚ，Ｓａｎ　Ｄｉｅｇｏ，ＣＡ，ＵＳＡ）．１３－ｔｕｂｕｌｉｎ（ＢＤ　Ｂｉｏｓｃｉｅｎｃｅｓ）　ｗａｓ　ｕｓｅｄ　ｔｏ　ｎｏｒｍａｌｉｚｅ　ｔｈｅ　ｑｕａｎｔｉｔｙ　ｏｆ　ｔｈｅ　ｐｒｏｔｅｉｎ　ｏｎ　ｔｈｅ　ｂ】ｏｔ．　２．８　Ｓｔａｔｉｓｔｉｃａｌ　ａｎａｌｙｓｉｓ　Ａｌｌ　ｈｅ　ｍｅａｓｕｒｅｍｅｎｔｔ　ｄａｔａ　ｗｅｒｅ　ｎａｌａｙｚｅｄ　ａｎｄ　ｅｘｐｒｅｓｓｅｄ　ａｓ　ｔｈｅ　ｍｅａｎ±ＳＤ．Ｒｅｓｕｌｔｓ　ｗｅｒｅ　ｃｏｎｓｉｄｅｒｅｄ　ｓｉｇｎｉｉｃａｎｔｆ　ｉｆ　Ｐ＜０．０５　ｗａｓ　ｏｂｔａｉｎｅｄ　ｕｓｉｎｇ　ａｎ　ａｐｐｒｏｐｒｉａｔｅ　ａｎａｌｙｓｉｓ　ｏｆ　ｖａｒｉａｎｃｅ　ｐｒｏｃｅｄｕｒｅ　ａｎｄ　ｕｎｐａｉｒｅｄ　ｔ－ｔｅｓｔ．　ｄｅｔｅｒｍｉｎｅ　ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ｏｆ　Ｆａｓ　ｎｄ　ＦａｓＬ　ｒＢＤ　Ｂｉｏｓｃｉｅｎｃｅｓ．ａ　Ｓａｎ　Ｄｉｅｇｏ，ＣＡ．ＵＳＡ）．　２．５　ＤＮＡ　ｆｒａｇｍｅｎｔａｔｉｏｎ　ａｓｓａｙ　Ｔｈｅ　ｃｅｌｌｓ　ｔｒｅａｔｅｄ　ｗｉｔｈ　ｄｉｆｆｅｒｅｎｔ　ｃｏｎｃｅｎｔｒａｔｉｏｎｓ　ｏｆ　ｅｍｏｄｉｎ　ｆｏｒ　４８　ｈ　ｗｅｒｅ　ｈａｒｖｅｓｔｅｄ．ＤＮＡ　ｗａｓ　ｐｒｅｐａｒｅｄ　ｕｓｉｎｇ　ｔｈｅ　ｐｒｏｔｏｃｏ１　ｄｅｓｃｒｉｂｅｄ　ｂｙ　ｇｅｎｏｍｉｃ　ＤＮＡ　ｐｕｒｉｆｉｃａ．　ｔｉｏｎ　ｋｉｔ　ｆＳｈｅｎｅｒｇｙ　Ｂｉｏｃｏｌｏｒ　ＢｉｏＳｃｉｃｎｃｅ＆Ｔｅｃｈｎｏｌｇｙ　Ｃｏｍｐａｎｙ，Ｓｈａｎｇｈａｉ，Ｃｈｉｎａ），ｄｉｓｓｏｌｖｅｄ　ｉｎ　ＴＥ　ｂｕｆｆｅｒ．ｓｕｂ—　ｉｅｃｔｅｄ　ｔｏ　２％ａｇａｒｏｓｅ　ｇｅ１　ｅ１ｅｃｔｒｏｐｈｏｒｅｓｉｓ　ａｔ　５０　Ｖ　ｆｏｒ　４０　ｍｉｎ，ｓｔａｉｎｅｄ　ｗｉｈ　ｔｅｔｈｉｄｉｕｍ　ｂｒｏｍｉｄｅ，ｔｈｅｎ　ｐｈｏｔｏｇｒａｐｈｅｄ　３　Ｒｅｓｕｌｔｓ　ｕｎｄｅｒ　ｕｌｔｒａｖｉｏｌｅｔ　ｆＵＶ）ｌｉｇｈｔ．　．１　Ｅｍｏｄｉｎ　ｉｎｈｉｂｉｔｅｄ　ｔｈｅ　ｐｒｏｆｉｌｅｒａｔｉｏｎ　ｏｆｐｒｏｓｔａｔｅ　ｃａｎ．　Ｗｅ　ｆｉｒｓｔ　ｅｘａｍｉｎｅｄ　ｔｈｅ　ｅｆ＿ｆｅｃｔ　ｏｆ　ｅｍｏｄｉｎ　ｏｎ　ｐｒｏｓｔａｔｅ　ｃｅｒ　ｃｅｌｌｓ　２．６　Ｒｅｖｅｒｓｅ　ｔｒａｎｓｃｒｉｐｔａｓｅ　ｐｏｌｙｍｅｒａｓｅ　ｃｈａ　ｒｅａｃｔｉｏｎ　ｆ　ＲＴ－　ＰＣＲ１　ａｎａＩｖｓｉｓ　Ｔｏｔａｌ　ＲＮＡ　ｗａｓ　ｅｘｔｒａｃｔｅｄ　ｆｒｏｍ　ｔｒｅａｔｅｄ　ＬＮＣａＰ　ｃｅｌｌｓ　ｃａｎｃｅｒ　ｃｅｌｌ　ｐｒｏｌｉｆｅｒａｔｉｏｎ．ＬＮＣａＰ　ｃｅｌｌ　ｇｒｏｗｔｈ　ｗａｓ　ｃｈｅｃｋｅｄ　ｉｎ　ｔｈｅ　ｐｒｅｓｅｎｃｅ　ｏｆ　ｖａｒｉｏｕｓ　ｃｏｎｃｅｎｔｒａｔｉｏｎｓ　ｏｆ　ｅｍｏｄｉｎ　ｕｓ．　ｉｎｇ　ＭＴＴ　ａｓｓａｙ．ＭＴＴ　ｒｅｓｕｌｔｓ　ｓｈｏｗｅｄ　ｔｈａｔ　ｈｅ　ｃｅｌｌｔ　ｇｒｏｗｔｈ　ｗａｓ　ｉｎｈｉｂｉｔｅｄ　ｂｙ　ｅｍｏｄｉｎ　ｉｎ　ａ　ｄｏｓｅ．．ｄｅｐｅｎｄｅｎｔ　ａｎｄ　ｔｉｍｅ．．　ｕｓｉｎｇ　Ｔ　ｚｏ１　ｒｅａｇｅｎｔ（ＭＢＩ　Ｆｅｒｍｅｎｔａｓ，Ｂｕｒｌｉｎｇｔｏｎ，Ｏｎｔａｒｉｏ，　Ｃａｎａｄａ）ｆｏｌｌｏｗｉｎｇ　ｔｈｅ　ｍａｎｕｆａｃｔｕｒｅｒ’ｓ　ｉｎｓｔｒｕｃｔｉｏｎｓ，ａｎｄ　ａ　ｐｏｒｔｉｏｎ　ｏｆ　ｔｏｔａｌ　ＲＮＡ（２　ｇ）ｗａｓ　ｔｒａｎｓｃｒｉｂｅｄ　ｒｅｖｅｒｓｉｂｌｙ　ｗｉｔｈ　ｔｈｅ　Ｍ．ＭｕＬ　Ｖ　ｒｅｖｅｒｓｅ　ｔｒａｎｓｃｒｉｐｔａｓｅ　ｉｎ　ｔｈｅ　ｐｒｅｓｅｎｃｅ　ｏｆ　ａ　ｒａｎｄｏｍ　ｈｅｘａｍｅｒ　ｐｒｉｍｅｒ．Ｔｈｅ　ｒｅｓｕｌｔｉｎｇ　ｃＤＮＡ　ｐｒｅｐａ．　ｄｅｐｅｎｄｅｎｔ　ｍａｎｎｅｒ　ｆＦｉｇｕｒｅ　１Ａ）．Ｏｂｓｅｒｖａｔｉｏｎ　ｏｆ　ｍｏｒｐｈｏ．　１ｏｇｉｃ　ｃｈａｎｇｅｓ　ａｌｓｏ　ｓｈｏｗｅｄ　ｔｈａｔ　ｔｈｅ　ｎｕｍｂｅｒ　ｏｆ　ＬＮＣａＰ　ｃｅｌｌｓ　ｄｅｃｒｅａｓｅｄ　ａｎｄ　ａｌｔｅｒｅｄ　ｉｎ　ｍｏｒｐｈｏｌｏｇｉｃ　ｃｈａｒａｃｔｅｒｉｓｔｉｃ　ｏｂｖｉｏｕｓｌｙ　ａｆｔｅｒ　ｂｅｉｎｇ　ｃｕｌｔｕｒｅｄ　ｗｉｔｈ　ｅｍｏｄｉｎ．Ｔｒｅａｔｍｅｎｔ　ｗｉｔｈ　ｄｉｆｆｅｒｅｎｔ　ｃｏｎｃｅｎｔｒａｔｉｏｎｓ　ｏｆ　ｅｍｏｄｉｎ　ｆｏｒ　４８　ｈ　ｒｅｓｕｌｔｅｄ　ｉｎ　ｃｅｌｌ　ｓｈｒｉｎｋａｇｅ，ａ　ｒｏｕｎｄｅｄ　ｍｏｒｐｈｏｌｏｇｙ　ａｎｄ　ｆｕｚｚｙ　ｃｅｌｌ　ｂｏｕｎｄａｒｙ，ａｎｄ　ｅｖｅｎｔｕａｌｌｙ　ｃｅｌｌｓ　ｄｅｔａｃｈｅｄ　ｆｒｏｍ　ｔｈｅ　ｒａｔｉｏｎ　ｗａｓ　ｓｕｂｊｅｃｔｅｄ　ｔｏ　ＰＣＲ　ａｍｐｌｉｉｆｃａｔｉｏｎ　ｕｓｉｎｇ　ａ　ＰＣＲ　ｋｉｔ　ｆｒｏｍ　ＴａＫａＲａ　Ｂｉｏｔｅｃｈ．Ｄａｌｉａｎ，Ｃｈｉｎａ．Ｔｈｅ　ｐｒｉｍｅｒｓ　ａｎｄ　ａｎｎｅａｌｉｎｇ　ｔｅｍｐｅｒａｔｕｒｅ　ａｒｅ　ｓｈｏｗｎ　ｉｎ　Ｔａｂｌｅ　１．Ｔｈｅ　ＰＣＲ　ｐｒｏｄｕｃｔｓ　ｗｅｒｅ　ａｎａｌｙｚｅｄ　ｂｙ　ｅ１ｅｃｔｒｏＤｈｏｒｅｓｉｓ　ｏｎ　ａ　Ｔｅｈ＋８６－２１・－５４９２－２８２４；Ｆａｘ：＋８６－２１－・５４９２－２８２５；ＳｈａｎｇｈａＬ　Ｃｈｉｎａ　６２７．　维普资讯 http://www.cqvip.com

Ｅｍｏｄｉｎ　ｉｎｄｕｃｅｓ　ａｐｏｐｔｏｓｉｓ　ｉｎ　ＬＮＣａＰ　ｃｅｌｌ　Ａ　１２Ｏ　Ｂ　１２０　１ＯＯ　、－，　１ＯＯ　８Ｏ　８０　兰　．兰　Ｄ　ｏ　．雹　＞　０　垩　６ｏ　６０　＝　０　ｏ　０　４０　４Ｏ　２Ｏ　２０　Ｏ　１Ｏ　２Ｏ　３Ｏ　４０　Ｏ　２４　ｈ　４８　ｈ　７２　ｈ　Ｃｏｎｃｅｎｔｒａｔｉｏｎ　ｍｏｌ／Ｌ　Ｆｉｇｕｒｅ　１．Ｅｆｆｅｃｔｓ　ｏｆ　ｅｍｏｄｉｎ　ｏｎ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌ　ｐｒｏｌｉｆｅｒａｔｉｏｎ．（Ａ）：Ｔｉｍｅ—ａｎｄ　ｄｏｓｅ—ｄｅｐｅｎｄｅｎｔ　ｉｎｈｉｂｉｔｏｒｙ　ｅｆｆｅｃｔｓ　ｏｎ　ＬＮＣａＰ　ｃｅｌｌ　ｇｒｏｗｔｈ．　ＬＮＣａＰ　ｃｅｌｌｓ　ｗｅｒｅ　ｔｒｅａｔｅｄ　ｗｉｔｈ　０．０　ｌ％ｄｉｍｅｔｈｙｌ　ｓｕｌｆｏｘｉｄｅ（ＤＭＳＯ）ｏｒ　ｖａｒｉｏｕｓ　ｃｏｎｃｅｎｔｒａｔｉｏｎｓ　ｏｆ　ｅｍｏｄｉｎ（１　０，２０，３０　ａｎｄ　４０　ｌａｍｏＩ／Ｌ）：（Ｂ）：　ＬＮＣａＰ　ｎｄ　ａＰＣ一３　ｃｅｌｌｓ　ｗｅｒｅ　ｒｅａｔｔｅｄ　ｗｉｍ　ＤＭＳＯ　ｏｒ　４０￣ａｒｎｏｌ／Ｌ　ｅｍｏｄｉｎ．Ｃｅｌｌｓ　ｗｅｒｅ　ｃｕｌｔｕｒｅｄ　ｆｏｒ　４８　ｈ　ｉｎ　９６一ｗｅｌｌ　ｐｌａｔｅｓ．ａｎｄ　ｔｈｅｎ　ｒｅａｔｅｄ　ｔｗｉｔｈ　ｅｍｏｄｉｎ　ｉｎ　ｔｈｅ　ｐｒｅｓｅｎｃｅ　ｏｆ　１０％ｓｅｒｕｍ　ａｔ　３７￣Ｃ　ｆｏｒ　ｄｉｆｆｅｒｅｎｔ　ｈｏｕｒｓ（２４．４８　ａｎｄ　７２　ｈ）．Ｔｈｅ　ｖｉａｂｌｅ　ｃｅｌｌｓ　ｗｅｒｅ　ｍｅａｓｕｒｅｄ　ｕｓｉｎｇ　ＭＴＴ　ａｓｓａｙ　ａｎｄ　ｈｅ　ｔｆｒａｃｔｉｏｎ　ｏｆ　ｖｉａｂｌｅ　ｃｅｌｌｓ　ｗａｓ　ｃａｌｃｕｌａｔｅｄ　ｂｙ　ｄｅｆｉｎｉｎｇ　ｔｈｅ　ａｂｓｏｒｐｔｉｏｎ　ｏｆ　ｃｏｎｔｒｏｌ　ｃｅｌｌｓ　ａｓ　ｌ　００％．ＡＵ　ｄｅｔｅｒｍｉｎａｔｉｏｎｓ　ａｒｅ　ｅｘｐｒｅｓｓｅｄ　ａｓ　ｈｅ　ｍｅａｔｎ　ｐｅｒ　ｃｅｎｔ　ｃｏｎｔｒｏｌ±ＳＤ．Ｍｅａｎｓ　ｗｅｒｅ　ｆｒｏｍ　ｔｈｒｅｅ　ｉｎｄｅｐｅｎｄｅｎｔ　ｅｘｐｅｒｉｍｅｎｔｓ．ｅａｃｈ　ｃｏｎｔａｉｎｉｎｇ　ｔｒｉｐｌｉｃａｔｅ　ｍｅａｓｕｒｅｓ．　６２８　，，ｆｔｏ：／／ｗｗｗ．ａｓｉａａｎｄｒｏ．ｃｏｍ；ａｊａ＠ｓｉｂｓ．ａｃ．ｃｎ　维普资讯 http://www.cqvip.com

AsianJAndrol2008；4)：62510《—634Contro10pmol／L20pmol／L30i~mol／L40pmol／LFigureu2．Emodininduced—cellmorpincbatedinserumathemediumcontahologicchangesofLNCaPcellsLNCaPcellswerecultured48hbeforeemodintreatmentsCellsr01)ordifferentconcentrationsofemodinfor48hinthepresenining001％dimethylsulfoxide(cont．．．wereceof10％t37C。(Magnification：x100)．substratummw．．Incontrasts．cellsincithaubatedintheacontroltheexpressionosfPSAexwasalsodeteormanined．Theresultsdmediuerewellprea，dwlfttenenadmorohologyiohowedthattheanpressionfARodPSAdecrease(Figuere21Moeanwhilewea—lsostudiedthe一iprolffat．~：rativeusfFigure5A1inconanaresureasedtheexpressionffectfemo．dinTheinARleresussPC3ecellsvari(Figure5B)signifd．cantlyashteemfp53andp21increasedodinconcentrationsweretheessconcentrationsltsshow—dthatPC3cellswereTodeanmonstratefurtherinexffects，ofemodinmoreeresistanttotheceemodinmediated．antiproferativeAR，p53wdD21protepreionWlestemblot．ffectthanLNCaPlls(FigllurelBllysisasusedtoevaluatetheirpro5CdemdecreasonsteinlevelsTheex—ltsillustratedinFiguretrateandthattheig32．EmodinindueccedceapoptosisinLNCaPcecellscepressionofARprofp53emoexteinwasseddthafttheexsn—TodetermintheapoptosisofLNCaPllsindud．pressionoan．dp2lproteincons．wasincreasedifi—byemodin，lfowytomcarretricanalysisanout．dDNAfragwcmencan．tlymbydinistentwith，theeweffectoemodintationaassaywereiedUsingfloaytometry．onRNApressionnThereforeoconcludedthatthedbyaemopoptosis．wasconifrmedbytheroseppearathenceofasubGn1proliferativmeinhibitiofLNCaPancellindu．cedinpeakemoTheapoptosisratereacasconcenumastratioum0OfightbeErelatedtotheARdp53p2lpathw3y．dininsucreaseeststdandhed．．amaximat401／Lse．Thisgghatureemodininduced．poptoaisllswasdo．．34．modinenhacncedracaspase一．and．9expressionanddependent(Figturemar3A)WhenLNCtratiOnsoPcewerecul—in．creasedBax／Bl2一tioinLNCaPcelIsadwithvariouasconcenfemodinfor48haTherearetwotypica一lapoptosispathwvo．．ys：dea一th，kedDNAfrmannergmentationwasobs3Berve，dindosede——ligcasand／re．．cependentan(Figure4A)．Howures．everthesubG。1peal(tdeathinducpase一ptor(Fas)ingsignal)mmediatedc(inalvingceandhemiclindupase8d(involvingcas—dDNAfragmentationfFigceand4B)wereno9，foundinthetreatedPC3一llsvesatigatethesitochondrialpathway)apoptosisT0inpathwaysofemodininducedLNCaPcells．．poptocis，theexanpressioas，nofcasrm33E．modindecreasedtheexpressionofARandPSA．andBl2一，FasdFLwasdete8and9pase3inedAfter48h一一一，，Bax—，．treatincreasedtheexpressionofp53andp21in乙NCnPcellsmentwithdemousdintheexpressionocfFasandFasLwasTheARplaycesan．llproliferationssoranimportantroleintheprostatedp53geneisanextensivetumtothecancerorsumeasureingflexowressytomnetry．Thereanwerenodiffer-een．p—encesconofthecepioofFaasdFllsasLbetwthepretarthatcanneleadtf／tip’inductionofadownanstreamtrolllsuseandemodintretedexrce(Figure61noRT-．getgerowtp21．”a’toinhibitthwecellcyclethedcausecensllfPCR一was一dtodete．rminetheasaexpressiofcaspase3en，gharrestTodetermineemohetherraemeinhibitioo8and9B，axBcl2一nadFfte48hemodintreatmpase3一t．thece一llproliferationbyadinwasandiatedbyARmreandd．The一resultsseshow．edthatthe一pressionasofcasandp53p21pathwexys，ImPCRperfodtodetectthe9increaemodCaspase8trationceansdFhadasealmostnocurehanges．pression1evelsofAR．p53dp21inememodin—treateoasdinocOncenincredfFig7A1Exo．LNCaPcells．BecausethePSAisthajortargetfARposurefLNCaPllstodifferentconcentrationsfTel：+862154922824；F󰀀󰀀ax：+862154922825；ShanghaiChina629󰀀维普资讯 http://www.cqvip.com

EmodininducesapoptosisinLNCaPcell3A00∞00寸00n00N00l_0．JmDE3z0∞l_000．I∞DE丁z．10clE3z00no卜N00∞00寸00n00No00r000寸0Nn0寸No∞I．10Bm∞Dl／L∞DE丁E3a)DE3ZZl‘乙50Z050100DNAcon150tent2002500100DNA150conten200t250050100DNA150con200250tent00N{1．00寸00n00N00I．o三8Er00旧00寸00n00N00广J丁Tjlrrjj_o00∞00甘00n00N广T]^rrjj。1l-Z昌O∞O∞LO50100DNAII1…P-O_n“050100150con200250^T150t200250，mO，一1■1-1DNAtentcontenL叫000寸00n00N001．0∞D00m00寸oon00N00I．0E3DE3ZZkO。一50100DNA150conten200t250050100DNAcon150tent200250050100DNA150con200250tentd)DE：Z050100DNAcon150ten200250O50100DNA150t200250tcontenFigurc3．Effectsceof．emodinonpeakinLNCaPwlls(B)：EffecsulowcytoprostatecancercellapoptosisinftsofemodinonPC3cellsapoptosisCells一metryassayre．(A)：Emorodininducedtheemoa．werecultu，d48hbefore，dintreatmppearanceCellsents．ofasubG—iwerereatetadtith001％dim．ethylrlfoxide(contrdintea01)，ordifferentwereconcentrationansofemodin(10owc2030mece40~noL)intheprel／．senceofl0％dseFLlmusin370Cfocr48h．AfterwemotmentcellsharvesteddsulbjectedtofgeoytotncanalysisApoptosiswasmeasureycleesuanalysisreRltsareithpropidiumiodide(PI)stainingandthepehreeindependentexperimentspresentativeoftrcentafhypodiploidlls(apoptoticpopulationofcells)wascalcugcelllated󰀀．󰀀630󰀀，，ftp：llwww．asiaandro．com；aja@sibs．aCcn，维普资讯 http://www.cqvip.com

AsianJAndro，2008；10一J?625634—A100bpA!!里垫里呈兰里!Bmol／Li竺!!!!!!!!!!!!!!叵_I_三至!三)量熏100．RlA陋．ctin一500bp083．081．065．250．󰀀—󰀀~AR／IPSA【actin󰀀—-󰀀—-󰀀—-󰀀--1000bp100．O88．0．76065．054PSNI~actin3000bpB010203040Bmol／L厂===_-==Marker『_-=_-‘二iip53‘_i010203040‘233．3jii一1299．actin~mollL100．1_74194．~1p53／actinB!=100bp100．!!457．!!!!!!533．Jp2131p21／253．715actinC500bp010203040pmol／LAR1000bp3[1tubulin一3000bp072．O67．05．042．3tubulinAR／1p531117．136．144．154．Btubulinp21，p21Marker0dinon102030cancerce．40pamol／L1118．163．206．208．3tubulin1p21／󰀀Figeure4．Effectsofemoprostateallpoptosisinthedininara—Figreure5．iEfnecectso，femo，dinonantheexpressionolectrophoresisceassayofDNAfrogmentationmenon(A)：EmolatedgedfBlARePSAop53dp2lonmna．t／／cip0infproliferationLNCaPcells(A)．duadtheappearancefDNAfrag．tationfahallmkofanusc：Theffects．femodinRNAlenormaanvelse”aweredetectedpoptosis)inLNCaPcells(B)：EanceofcellularnecrosisinPC3一mocedin．lyinducedthewere．llsCellsfculture20ppeard48hethingRT．PCR．31teactinwasousedto，lizthequantityoffl／eip’DNAd(C)：ProingwesteinrnlevelsblotofARp53，dp2l一weremea—beforesuemodintreadifitment．thenweretreatedwitlloemoat00l％dim，，ylsureusanalysistein．an3tubulind1werewasusedtowlfoxide0orerentconcentrationssenceodin(10。30．andr—norma．lizethequethan．antityfporroCellsincubatedith40pmphoex1／L1inthepre，f10％danserum37Cfor48hAfte001％dimylsulfoxidemodifferentcOncentrationsoncefemodinantreatmentscells．wereharvltsesteredsubjectedtoDNAelectron(10。，20，30d40laResuL)inthepresel／arereDresenof10％serumttresisanaentslysis．Resuarepresentativeofthreeindepedent37Cfor48hexiperments．ltstativeofthreeindependeperimemodinoresultedintheincrel2levels一aseoofBfeaxlevelsandthede。Pha．rmacological，studieshavedeira，monstrateandthatlaemoxandincreasefB，cafter48hstreatment(Figure7B)ahasantitumor—antibacteldiureticcausereasedvasoretefThereforetheatheabovedatahowdthamtemodininducedyfects『8101ee．Emondind．cananamarakeddecreaseiny．poptosisofLNCaPusingainsteadofadeathinducingsign󰀀itochondrialpathw．llproliferatiofuterineeanincinpoptosisin，mancanaltypesocerancancercellsincludinglungcancer，cancer．breastudcervixf22231Altholarmeccghithas．4Discussionbeenpalmclaimdtohave，potentanticanceractivityinprossotatecancercells111the『llmolecuehanismfemo．hTnesemaemeherbRheumatumnhasbeenearsm．usedasaChidinthace．tproducenitsbiologicalwee．ffetsinprostateTheprescancerdicineformorethaotenyEmodinisthellshasvesnotabeecharacterizedn．entstudyjor+activeconstituentfRheupalmatum67】【，intigtedtheffectsandmechaismsofemodininTeh862154922824；Fax：+862154922825；Sh󰀀-󰀀-angha~China󰀀631维普资讯 http://www.cqvip.com

EmodininducesapoptosisinLNCaPcellA010203040umo．l／LpastineCa∞仁3∽s9亡3ooac0oCassspasee9／p3actinCa10’pas一10010010‘10010’102100100100Ca3[pase3／󰀀actinFLlH一FLlH一Ca0CaFa100．ssspasee一8󰀀AB∞lu30pas󰀀8／31actin123095．126．119．Fas3／[一actin们C3Bo●——●-lO●—●—●20●■●—I—30—40一pmol／L0一Bcl2．0●—一■—-●—-●—一●●—■BB󰀀actin1OO．084．078．031．O-23c10FL2H一’100100一10‘100l2／p󰀀actinFL2H100．Bax188．213．350．444．Bax／3一actinCFigecureDo6．EffectsemofemodinontheexonpressionanofFasandFasL．TheowFiggure7．Effectsofemo．dineonhteexopressionofapoptosisrelatedfectsofL)din(40larnol／F．asdFasLwereweredetectedbyflw．eneinLNCaPcellsTheffectsfemodinweredetected．usingac—ytometryassayeinLNCaPcellsCellsincubatedi山001％dinintheasn—reversetranscriptasepolymerasechainreaction(ImPCR)．Be—dimthylsulfoxideeo(DMSO)(contr01)aor．L40~lnl01／tinwasuseodtoonnormalizeemothequantityofcDNA，fA)Theaseffectsasenapresencemof10％serum—t370Gfor48h—fA)：Fasdin．—control；03)：Ffemodin．theexpressionofCaspase9eeCasp3，Cascp一8ddin；(C)：FasLcontrol；(D)：FasLexemoResultsan—dF．ashfB)Twereffectsfofwemodin．onhteeexarerepresepressionofBl2tativeofthreeindependentipreBaxCellsincubatedoith001％dim．ments．entconcentrationsemoatdinf10。20．ferhylsulfoxideordiflt30and40pmol，L)intheResupresenceoof10％serum37Cfor48hments．．ltsarcrepresentativefthreeindependentexiperhumanprostatecancercevo．lllinesLNCaP．ARishighlyincancerresverawerelvedintheprolifeyplantcanrationaofprosta，teasce24】Mlls【，anhemicdgumlssuchbyemodincouldene，reduaceLNCaPmorcellproliferationgeneex．．trol[251quercetin[26]asmastic[27]scrThep53gistusurepprguessorAsatrann—reportedessprostatecancerexpotentialchembecauseoftheirBiancoarraoe．preventiveagentsforffectsoninhibitionof，iptionfaclgtorp53proteincontrolatesthevoanpressioceocfseverarowt，hlg，enesinlvdnaedinllcyleARprioon．lellayetabyganalysisffmicrosomenceren，reportedthat1[2829】luencetheagentscaninfprogressionDNArepairapoptosis161Theactivationofp53canca．usegiogenesis[14_inductionofp2l，，rowthoftheprostatecaocellsbytamoexpression．severalandrogmebolicdulatingthegenestheAR．which，asthecyclindepe—ndentkinaseinhibitoraninturn—inhibitsDNAnasereplication321『an．dcyclindependentkicoregulato．rs(AR：CCNDl)signaltransductionre—latedre(CDK)G2c一cyclinactivity，darreststhece，llcycleathtegenes(egERBB2．．．；VCAM；SOSl．)andandrogenguoan—Glorlatedgenes(egPSA)PSAisamajortargetgenARwhichinducesPSAexpressionthroughthree．ef—p53oan3334]Inourstudytheincreaseinheckpoint『dp21expressionmightcontributetotheinhibitionllproliferafthecetioninducedbyoemodin．drogpromsen．responsiveelementslocateoterofthePSAg，ene[30ess，dintheproximal6kb31】WhenARexpres—Apoptosisisamajorformtanfcelldeaththemandessenancetialo．forhomcnormalde．velopdmen，dforaintenf，iondecreasedPSAnreexuprionalsodecdin．reased．AsaeostasisotheraInaandditionracurrentantineoplastictherapiesresualtofARdowglationbyperimpressionemo．PSA，expressionhempyadiationtherapyarenclikelytobes．aflsodecreasedininhibitionourexoentThereforethatthefexandfunctionitislikelyoftheARfectedbythecessopoptotictendeuiesofcells；thusthispro。bvioushastherapeticimplication[35]During632．w，，ftp：l／ww．asiaandro．corn；aja@sibs．ac．cn维普资讯 http://www.cqvip.com

Ａｓｉａｎ　Ｊ　Ａｎｄｒｏｌ　２００８；１０　ｌ４１：６２５—６３４　印ｏｐｔｏｓｌｓ，ｃｅｒｔｍｎ　ｃｈａｒａｃｔｅｒｉｓｔｉｃ　ｍｏｒｐｈｏｌｏｇｉｃ　ｅｖｅｎｔｓ，ｓｕｃｈ　Ａｃｋｎｏｗｌｅｄｇｍｅｎｔ　ａｓ　ｎｕｃｌｅａｒ　ｃｏｎｄｅｎｓａｔｉｏｎ，ｎｕｃｌｅａｒ　ｆｒａｇｍｅｎｔａｔｉｏｎ　ａｎｄ　ｃｅｌｌ　ｓｈｒｉｎｋａｇｅ．ａｎｄ　ｂｉｏｃｈｅｍｉｃａｌ　ｅｖｅｎｔｓ．ｓｕｃｈ　ａｓ　ＤＮＡ　Ｔｈｉｓ　ｓｔｕｄｙ　ｗａｓ　ｓｕｐｐｏｒｔｅｄ　ｂｙ　ｔｈｅ　Ｎａｔｕｒａｌ　Ｓｃｉｅｎｃｅ　ｆｒａｇｍｅｎｔａｔｉｏｎ，ｏｃｃｕｒ［３６］．Ｉｎ　ｔｈｅ　ｐｒｅｓｅｎｔ　ｓｔｕｄｙ，ｔｈｅ　ｍｏｒ—　ｐｈｏｌｏｇｉｃａｌ　ｃｈａｎｇｅｓ　ｗｅｒｅ　ｏｂｓｅｒｖｅｄ，ｉｎｃｌｕｄｉｎｇ　ｃｅｌｌ　ｓｈｒｉｎｋ—　ａｇｅ　ｉｎ　ｅｍｏｄｉｎ．ｔｒｅａｔｅｄ　ＬＮＣａＰ　ｃｅｌｌｓ．ｓｕｂ。Ｇ１　ｐｅａｋ　ｆｏｒｌＴｌａ．　Ｆｏｕｎｄａｔｉｏｎ　ｏｆ　Ｓｈａｎｄｏｎｇ　Ｐｒｏｖｉｎｃｅ（Ｎｏ．Ｙ２００５Ｃ２９）ａｎｄ　ｔｈｅ　Ｎａｔｉｏｎａ１　Ｎａｔｕｒａｌ　Ｓｃｉｅｎｃｅ　Ｆｏｕｎｄａｔｉｏｎ　ｏｆ　Ｃｈｉｎａ　ｆＮｏ．　３０４７０８２０　ａｎｄ　Ｎｏ．３０６７０５８ｌ、．　ｔｉｏｎ　ｉｎ　ｌｆｏｗ　ｃｙｔｏｍｅｔｒｙ　ａｎａｌｙｓｉｓ　ｎｄ　ａｃｅｌｌ　ｄｅａｔｈ　ｒＮｎ　ａｓｓａｙ）．　Ｔｈｅ　Ｂｃ１。２　ｆａｍｉｌｙ　ｐｒｏｔｅｉｎｓ　ｃｏｎｓｔｉｔｕｔｅ　ｉｍｐｏｒｔａｎｔ　ｃｏｎ．　ｔｒｏｌ　ｍｅｃｈａｎｉｓｍｓ　ｉｎ　ｔｈｅ　ｒｅｇｕｌａｔｉｏｎ　ｏｆ　ａｐｏｐｔｏｓｉｓ．Ｓｏｍｅ　ｍｅｍｂｅｒｓ　ｏｆ　ｔｈｉｓ　ｆａｍｉｌｙ，ｓｕｃｈ　ａｓ　Ｂｃ１．２　ａｎｄ　Ｂｃ１．ＸＩ，ｓｕｐ—　ｐｒｅｓｓ　ａｐｏｐｔｏｓｉｓ，ｗｈｅｒｅａｓ　ｏｔｈｅｒｓ，ｓｕｃｈ　ａｓ　Ｂａｘ　ａｎｄ　Ｂｉｄ，　ｐｒｏｍｏｔｅ　ａｐｏｐｔｏｓｉｓ．Ｔｈｅ　ｂａｌａｎｃｅ　ｂｅｔｗｅｅｎ　ｔｈｅｓｅ　ｔｗｏ　ｇｒｏｕｐｓ　ｄｅｔｅｒｍｉｎｅｓ　ｔｈｅ　ｆａｔｅ　ｏｆ　ｃｅｌｌｓ　ｉｎ　ｍａｎｙ　ａｐｏｐｔｏｓｉｓ　２　ＲｅｆｅＦｅｎｃｅｓ　Ｇｒｅｅｎｌｅｅ　ＲＴ，Ｍｕｒｒａｖ　Ｂｏｌｄｅｎ　Ｓ．Ｗｉｎｇｏ　ＰＡ．Ｔｈｅ　ｐｒｏｓｔａｔｅ：　ａｎ　ｉｎｃｒｅａｓｉｎｇ　ｍｅｄｉｃａｌ　ｐｒｏｂｌｅｍ．Ｐｒｏｓｔａｔｅ　ｌ９９０；１６：３９—４８．　Ｈａｎｋｓ　ＧＥ．Ｌｏｎｇ—ｔｅｒｍ　ｃｏｎｔｒｏｌ　ｏｆｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｗｉｔｈ　ｒａｄｉａｔｉｏｎ．　Ｐａｓｔ．ｐｒｅｓｅｎｔ．ａｎｄ　ｆｕｔｕｒｅ．Ｕｒｏｌ　Ｃｌｉｎ　Ｎ　Ａｍ　１９９６；２３：６０５－ｌ６．　Ｇａｒｎｉｃｋ　Ｍ｜Ｂ．Ｈｏｒｍｏｎａｌ　ｔｈｅｒａｐｙ　ｉｎ　ｈｅ　ｍａｔｎａｇｅｍｅｎｔ　ｏｆｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ：ｆｒｏｍ　Ｈｉｇｇｉｎｓ　ｔｏ　ｔｈｅ　ｐｒｅｓｅｎｔ．Ｕｒｏｌｏｇｙ　１９９７；４９：５一ｌ５．　４　ｓｙｓｔｅｍｓ［３７］．Ｉｎ　ｔｈｅ　ｐｒｅｓｅｎｔ　ｓｔｕｄｙ，ｅｍｏｄｉｎ—ｉｎｄｕｃｅｄ　ａｐｏｐｔｏｓｉｓ　ｏｆ　ＬＮＣａＰ　ｃｅｌｌｓ　ａｐｐｅａｒｅｄ　ｔｏ　ｂｅ　ａｓｓｏｃｉａｔｅｄ　ｗｉｔｈ　ｔｈｅ　ｉｎｃｒｅａｓｅｄ　ｅｘｐｒｅｓｓｉｏｎ　ｏｆ　Ｂａｘ　ａｎｄ　ｄｅｃｒｅａｓｅｄ　ｅｘｐｒｅｓ．　ｓｉｏｎ　ｏｆ　Ｂｃ１．２．Ｉｎｄｅｅｄ．ｔｈｉｓ　ｒｅｓｕｌｔ　ｉｓ　ｃｏｎｓｉｓｔｅｎｔ　ｗｉｔｈ　ｐｒｅｖｉ．　ＳｕｒｈⅥ．Ｃａｎｃｅｒｃｈｅｍｏｐｒｅｖｅｎｔｉｏｎ　ｗｉｈ　ｔｄｉｅｔａｒｙ　ｐｈｙｔｏｃｈｅｍｉｃａｌｓ．　Ｎａｔ　Ｒｅｖ　Ｃａｎｃｅｒ　２００３：３：７６８－８０．　Ｚｈａｎｇ　ＨＮ，　ｌ　ＣＸ，Ｚｈａｎｇ　ＰＪ，Ｃｈｅｎ　ＷＷ，Ｊｉｎｇ　ａＡＬ，Ｋｏｎｇ　Ｅ　ｅｔａ１．　Ｃｕｒｃｕｍｉｎ　ｄｏｗｎｒｅｇｕｌａｔｅｓ　ｈｏｍｅｏｂｏｘ　ｇｅｎｅ　ＮＫＸ３．１　ｉｎ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌ　ＬＮＣａＰ．Ａｃｔａ　Ｐｈａｒｍａｃｏｌ　Ｓｉｎ　２００７：２８：４２３－３０．　６　Ｔｓａｉ　ＴＨ．Ｃｈｅｎ　ＣＦ．Ｕｌｔｒａｖｉｏｌｅｔ　ｓｐｅｃｔｒｕｍ　ｉｄｅｎｔｉｉｃａｔｉｆｏｎ　ｏｆ　ｅｍｏｄｉｎ　ｉｎ　ｒａｂｂｉｔ　ｐｌａｓｍａ　ｂｙ　ＨＰＬＣ　ａｎｄ　ｉｔｓ　ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ　ａｐｐｌｉｃａｔｉｏｎ．Ａｓｉａ　Ｐａｃ　Ｊ　Ｐｈａｒｍａｃｏｌ　１９９２；７：５３－６．　７　ｏｕｓ　ｏｂｓｅｒｖａｔｉｏｎｓ　ｉｎ　ｗｈｉｃｈ　Ｂａｘ　ｏｖｅｒｅｘｐｒｅｓｓｉｏｎ　ａｎｄ　Ｂｃ１．２　ｄｅｃｒｅａｓｅ　ｉｎｄｕｃｅｄ　ｃｅｌｌ　ａｐｏｐｔｏｓｉｓ　ｄｕｅ　ｔｏ　ａ　ｖａｒｉｅｔｙ　ｏｆ　ｓｔｉｍｕｌｉ。　ｉｎｃｌｕｄｉｎｇ　ｃｈｅｍｏｔｈｅｒａｐｅｕｔｉｃ　ａｇｅｎｔｓ　ｓｕｃｈ　ａｓ　ｐａｃｌｉｔａｘｅｌ　ａｎｄ　ｏｒｉｄｏｎｉｎ［３８，３９］．　Ｃａｓｐａｓｅｓ，ａ　ｆａｍｉｌｙ　ｏｆ　ｃｙｓｔｅｉｎｅ　ｐｒｏｔｅａｓｅｓ，ｐｌａｙ　ａ　ｃｒｉｔｉ—　ｃａｌ　ｒｏｌｅ　ｉｎ　ｔｈｅ　ａｐｏｐｔｏｓｉｓ　ａｎｄ　ａｒｅ　ｒｅｓｐｏｎｓｉｂｌｅ　ｆｏｒ　ｍａｎｙ　ｏｆ　ｔｈｅ　ｂｉｏｃｈｅｍｉｃａｌ　ａｎｄ　ｍｏｒｐｈｏｌｏｇｉｃａｌ　ｃｈａｎｇｅｓ　ａｓｓｏｃｉ—　８　Ｌｉａｎｇ　ＪＷ．Ｈｓｉｕ　ＳＬ　Ｈｕａｎｇ　ＨＣ，Ｌｅｅ—Ｃｈａｏ　ＰＤ．ＨＰＬＣ　ａｎａｌｙｓｉｓ　ｏｆ　ｅｍｏｄｉｎ　ｉｎ　ｓｅｒｔｌｍ．ｈｅｒｂｓ　ａｎｄ　Ｃｈｉｎｅｓｅ　ｈｅｒｂａｌ　ｐｒｅｓｃｒｉｐｔｉｏｎｓ．Ｊ　Ｆ０ｏｄ　ＤｒｕｇＡｎａｌ　ｌ９９３：ｌ：２５１－７．　Ｋｏｙａｍａ　Ｍ．Ｋｅｌｌｙ　ＴＲ．Ｗａｔａｎａｂｅ　ＫＡ．Ｎｏｖｅｌ　ｔｙｐｅ　ｏｆ　ｐｏｔｅｎ—　ｔｉａｌ　ａｎｔｉｃａｎｃｅｒ　ａｇｅｎｔｓ　ｄｅｒｉｖｅｄ　ｆｒｏｍ　ｃｈｒｖｓｏｐｈａｎｏｌ　ａｎｄ　ｅｍｏｄｉｎ．　Ｓｏｍｅ　ｓｔｒｕｃｔｕｒｅ—ａｃｔｉｖｉｔｙ　ｒｅｌａｔｉｏｎｓｈｉｐ　ｓｔｕｄｉｅｓ．Ｊ　Ｍｅｄ　Ｃｈｅｍ　１９８８；３ｌ：２８３－４．　ａｔｅｄ　ｗｉｔｈ　ａｐｏｐｔｏｓｉｓ［４０］．Ｔｈｅｒｅ　ａｒｅ　ｔｗｏ　ｐｒｏｔｏｔｙｐｉｃａｌ　ｐａｔｈｗａｙｓ　ｆｏｒ　ｉｎｄｕｃｔｉｏｎ　ｏｆ　ａｐｏｐｔｏｓｉｓ　ｉｎ　ｍａｍｍａｌｉａｎ　ｃｅｌｌｓ　ｉｎｄｕｃｅｄ　ｂｙ　Ｂａｘ（ｉｎｖｏｌｖｉｎｇ　ｃａｓｐａｓｅ一９）ａｎｄ　Ｆａｓ（ｉｎｖｏｌｖｉｎｇ　ｃａｓｐａｓｅ一８　．Ｔｏ　ｉｎｖｅｓｔｉｇａｔｅ　ｔｈｅ　ｐａｔｈｗａｙ　ｏｆ　ｅｍｏｄｉｎ．ｉｎ—　ｄｕｃｅｄ　ＬＮＣａＰ　ｃｅｌｌｓ　ｄｅａｔｈ，ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ｌｅｖｅｌｓ　ｏｆ　ｃａｓｐａｓｅ．３，，８　ａｎｄ．９，Ｆａｓ　ａｎｄ　ＦａｓＬ　ｗｅｒｅ　ｄｅｔｅｒｍｉｎｅｄ　ｉｎ　ｏｕｒ　ｅｘｐｅｒｉｍｅｎｔ．ＲＴ．ＰＣＲ　ｒｅｓｕｌｔｓ　ｓｕｇｇｅｓｔ　ｔｈａｔ　ｔｈｅ　ｅｘ．　ｐｒｅｓｓｉｏｎ　ｏｆ　ｃａｓｐａｓｅ．３　ａｎｄ．９　ｉｎｃｒｅａｓｅｄ．ｂｕｔ　ｃａｓｐａｓｅ一８　ａｎｄ　Ｆａｓ　ａｌｍｏｓｔ　ｈａｄ　ｎｏ　ｃｈａｎｇｅｓ　ｉｎ　ＬＮＣａＰ　ｃｅｌｌｓ　ｗｉｔｈ　ｅｍｏｄｉｎ　ｔｒｅａｔｍｅｎｔｓ．Ｅｍｏｄｉｎ　ｉｎｄｕｃｅｄ　ＬＮＣａＰ　ｃｅｌｌ　ｄｅａｔｈ　９　Ｚｈｏｕ　ＸＭ．Ｃｈｅｎ　ＱＨ．Ｂｉｏｃｈｅｍｉｃａｌ　ｓｔｕｄｙ　ｏｆ　Ｃｈｉｎｅｓｅ　ｒｈｕｂａｒｂ．　ＸＸＩＩ．Ｉｎｈｉｂｉｔｏｒｙ　ｅｆｆｅｃｔ　ｏｆ　ａｎｔｈｒａｑｕｉｎｏｎｅ　ｄｅｒｉｖａｔｉｖｅｓ　ｏｎ　Ｎａ＋一　Ｋ　一ＡＴＰａｓｅ　ｏｆ　ｔｈｅ　ｒａｂｂｉｔ　ｒｅｎａｌ　ｍｅｄｕｌｌａ　ｎｄ　ａｔｈｅｉｒ　ｄｉｕｒｅｔｉｃ　ａｃｔｉｏｎ．　Ｙａｏ　Ｘｕｅ　Ｘｕｅ　Ｂａｏ　ｌ９８８；２３：ｌ７－２０．　ｌ０　Ｈｕａｎｇ　ＨＣ．Ｃｈｕ　ＳＨ．Ｃｈａｏ　ＰＤ．Ｖａｓｏｒｅｌａｘａｎｔｓ　ｆｒｏｍ　Ｃｈｉｎｅｓｅ　ｈｅｒｂｓ，ｅｍｏｄｉｎ　ａｎｄ　ｓｃｏｐａｒｏｎｅ，ｐｏｓｓｅｓｓ　ｉｍｍｕｎｏｓｕｐｐｒｅｓｓｉｖｅ　ｐｒｏｐｅｒｔｉｅｓ．Ｅｕｒ　Ｊ　Ｐｈａｒｍａｃｏｌ　ｌ９９ｌ：ｌ９８：２ｌｌ一３．　ｌｌ　Ｋ１ｕｃｋ　ＲＭ，Ｂｏｓｓｙ—Ｗｅｔｚｅｌ　Ｅ。Ｇｒｅｅｎ　ＤＲ．Ｎｅｗｍｅｙｅｒ　ＤＤ．Ｔｈｅ　ｔｈｒｏｕｇｈ　ａ　ｍｉｔｏｃｈｏｎｄｒｉａ１　ｐａｔｈｗａｙ　ｉｎｓｔｅａｄ　ｏｆ　ｔｈｒｏｕｇｈ　ａ　ｄｅａｔｈ—ｉｎｄｕｃｉｎｇ　ｓｉｇｎａ１．　Ｉｎ　ｓｕｍｍａｒｙ，ｔｈｅ　ｐｒｅｓｅｎｔ　ｓｔｕｄｙ　ｄｅｍｏｎｓｔｒａｔｅｄ　ｔｈａｔ　ｒｅｌｅａｓｅ　ｏｆ　ｃｙｔｏｃｈｒｏｍｅ　ｃ　ｆｒｏｍ　ｍｉｔｏｃｈｏｎｄｒｉａ：ａ　ｐｒｉｍａｒｙ　ｓｉｔｅ　ｆｏｒ　Ｂｃｌ一２　ｒｅｇｕｌａｔｉｏｎ　ｏｆ　ａｐｏｐｔｏｓｉｓ．Ｓｃｉｅｎｃｅ　ｌ　９９７；２７５：ｌ　ｌ　３２—６．　ｌ２　Ｈｏｖｅｍａｎ　ＭＳ，Ｄｅｍｉｎｇ　ＣＬ．Ｔｈｅ　ｈｅｔｅｒｏｌｏｇｏｕｓ　ｇｒｏｗｔｈ　ｏｆ　ｃａｎｃｅｒ　ｏｆ　ｔｈｅ　ｈｕｍａｎ　ｐｒｏｓｔａｔｅ．Ｓｕｒｇ　Ｇｙｎｅｃｏｌ　Ｏｂｓｔｅｔ　１９４８；８６：２９—３５．　ｌ３　Ｒｏｓｓ　ＲＫ，Ｂｅｒｎｓｔｅｉｎ　Ｌ，Ｊｕｄｄ　Ｈ，Ｈａｎｉｓｃｈ　Ｒ，Ｐｉｋｅ　Ｍ，Ｈｅｎｄｅｒｓｏｎ　ｅｍｏｄｉｎ　ｉｎｈｉｂｉｔｅｄ　ｔｈｅ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ａｎｄ　ｉｎｄｕｃｅｄ　ａｐｏｐｔｏｓｉｓ　ｏｆ　ＬＮＣａＰ　ｃｅｌｌｓ．Ｔｈｅ　ｇｒｏｗｔｈ　ｉｎｈｉｂｉｔｉｏｎ　ｏｆ　ＬＮＣａＰ　ｃｅｌｌｓ　ｉｎｄｕｃｅｄ　ｂｙ　ｅｍｏｄｉｎ　ｗａｓ　ｍｅｄｉａｔｅｄ　ｂｙ　ａ　ｄｅｃｒｅａｓｅ　ｉｎ　ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ａｎｄ　ｆｕｎｃｔｉｏｎ　ｏｆ　ｈｅ　ＡＲ　ａｎｄ　ａｔｎ　ｉｎｃｒｅａｓｅ　ｉｎ　ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ｏｆ　ｐ５３　ａｎｄ　ｐ２　１．Ｅｍｏｄｉｎ　ｉｎｄｕｃｅｄ　ａｐｏｐｔｏｓｉｓ　ｖｉａ　ｔｈｅ　ｍｉｔｏｃｈｏｎｄｒｉａｌ　ｐａｔｈｗａｙ．ａｓ　ｅｖｉｄｅｎｃｅｄ　ｂｙ　ｔｈｅ　ｉｎ．　ｃｒｅａｓｅｄ　ｅｘｐｒｅｓｓｉｏｎ　ｏｆ　ｃａｓｐａｓｅ．３．　９　ａｎｄ　ｉｎｃｒｅａｓｅｄ　Ｂａｘ／　Ｂｃ１—２　ｒａｔｉｏ．Ｉｔ　ｉｓ　ｐｒｏｐｏｓｅｄ　ｔｈａｔ　ｅｍｏｄｉｎ　ｍａｙ　ｂｅ　ａ　ｕｓｅｆｕｌ　ｃｈｅｍｏｐｒｅｖｅｎｔｉｖｅ／ｃｈｅｍｏｔｈｅｒａｐｅｕｔｉｃ　ａｇｅｎｔ　ｆｏｒ　ｐｒｏｓｔａｔｅ　ＣａｎＣｅｒ．　Ｂ．Ｓｅｒｕｍ　ｔｅｓｔｏｓｔｅｒｏｎｅ　ｌｅｖｅｌｓ　ｉｎ　ｙｏｕｎｇ　ｂｌａｃｋ　ａｎｄ　ｗｈｉｔｅ　ｍｅｎ．Ｊ　Ｎａｔｌ　Ｃａｎｃｅｒ　Ｉｎｓｔ　ｌ　９８６；７６：４５－８．　ｌ４　Ｖｏｇｅｌｓｔｅｉｎ　Ｂ，Ｌａｎｅ　Ｄ，Ｌｅｖｉｎｅ，ＡＪ．Ｓｕｍｎｇ　ｔｈｅ　ｐ５３　ｎｅｔｗｏｒｋ．　Ｎａｔｕｒｅ　２０００；４０８：３０７－１０．　ｌ５　Ｐｒｉｖｅｓ　Ｃ．Ｈａｌｌ　ＰＡ．Ｔｈｅ　ｐ５３　ｐａｔｈｗａｙ．Ｊ　Ｐａｔｈｏｌｏｇｙ　１９９９；ｌ８７：　ｌｌ２—２６．　ｌ６　Ｖｏｕｓｄｅｎ　ＫＨ．ｐ５３：ｄｅａｔｈ　ｓｔａｒ．Ｃｅｌｌ　２０００；ｌ０３：６９ｌ＿４．　ｌ７　Ｓｒｉｎｉｖａｓｕｌａ　ＳＭ，Ａｈｍａｄ　Ｍ。Ｆｅｒｎａｎｄｅｓ—Ａｌｎｅｍｒｉ　Ｔ．Ａｌｅｎｍｒｉ　ＥＳ．Ａｕｔｏａｃｔｉｖａｔｉｏｎ　ｏｆ　ｐｒｏｃａｓｐａｓｅ一９　ｂｙ　Ａｐａｆ－ｌ—ｍｅｄｉａｔｅｄ　ｏｌｉｇｏｍｅｒｉｚａｔｉｏｎ．Ｍｏｌ　Ｃｅｌｌ　ｌ　９９８；ｌ：９４９—５７．　ｌ８　Ｓｕｎ　ＸＭ，Ｍａｃｆａｒｌａｎｅ　Ｍ，Ｚｈｕａｎｇ　Ｊ。Ｗｏｌｆ　ＢＢ，Ｇｒｅｅｎ　ＤＲ．　Ｔｅｈ＋８６－２１・５４９２－２８２４；Ｆａｘ：＋８６－２１－ｓ４９２・２８２５；Ｓｈａｎｇｈａ￣Ｃｈｉｎａ　．６３３　维普资讯 http://www.cqvip.com

Ｅｍｏｄｉｎ　ｉｎｄｕｃｅｓ　ａｐｏｐｔｏｓｉｓ　ｉｎ　ＬＮＣａＰ　ｃｅｌｌ　Ｃｏｈｅｎ　ＧＭ．Ｄｉｓｔｉｎｃｔ　ｃａｓｐａｓｅ　ｃａｓｃａｄｅｓ　ａｒｅ　ｉｎｉｔｉａｔｅｄ　ｉｎ　ｒｅｃｅｐ—　ｔｏｒ—ｍｅｄｉａｔｅｄ　ａｎｄ　ｃｈｅｍｉｃａｌ—ｉｎｄｕｃｅｄ　ａｐｏｐｔｏｓｉｓ．Ｊ　Ｂｉｏｌ　Ｃｈｅｍ　１９９９；２７４：５０５３—６０．　１９　Ａｄａｍｓ　ＪＭ．Ｃｏｒｙ　Ｓ．Ｔｈｅ　Ｂｃｌ一２　ｐｒｏｔｅｉｎ　ｆａｍｉｌｙ：ａｒｂｉｔｅｒｓ　ｏｆ　ｃｅｌｌ　ｓｕｒｖｉｖａ１．Ｓｃｉｅｎｃｅ　１９９８；２８１：１３２２－６．　２０　Ｙ｛ｍｇ　Ｊ，Ｌｉｕ　Ｘ，Ｂｈａｌｌａ　Ｋ，Ｋｉｍ　ＣＮ，Ｉｂｒａｄｏ　ＡＭ，Ｃａｉ　Ｊ，ｅｔ　ａ１．　Ｐｒｅｖｅｎｔｉｏｎ　ｏｆ　ａｐｏｐｔｏｓｉｓ　ｂｙ　Ｂｃｌ一２：Ｒｅｌｅａｓｅ　ｏｆ　ｃｙｔｏｃｈｒｏｍｅ　ｃ　Ｃ１１ｉｌｌｅｒｎｊ　Ｇ．ｅｔ　ａ１．Ｖａｌｐｒｏｉｃ　ａｃｉｄ　ｉｎｄｕｃｅｓ　ｎｅｕｒｏｅｎｄｏｃｒｉｎｅ　ｄｉｆｅｒ－　ｅｎｔｉａｔｉｏｎ　ａｎｄ　ＵＧＴ２Ｂ７　ｕｐ—ｒｅｇｕｌａｔｉｏｎ　ｉｎ　ｈｕｍａｎ　ｐｒｏｓｔａｔｅ　ｃａｒｃｉ—　ｎｏｍａ　ｃｅｌｌｌｉｎｅ．Ｄｒｕｇ　Ｍｅｔａｂ　Ｄｉｓｐｏｓ　２００７：３５：９６８－７２．　３０　ＣｌｅｕｔｊｅｎｓＫ，Ｖａｎｄｅｒｌ（Ｈ，ＶａｎＥＣ，ＶａｎＲＨ，ＦａｂｅｒＰｗＴｒａｐｍａｎ　Ｊ．Ａｎ　ａｎｄｒｏｇｅｎ　ｒｅｓｐｏｎｓｅ　ｅｌｅｍｅｎｔ　ｉｎ　ａ　ｆａｒ　ｕｐｓ￣ｅａｍ　ｅｎｈａｎｃｅｒ　ｒｅｇｉｏｎ　ｉｓ　ｅｓｓｅｎｔｉａｌ　ｆｏｒ　ｈｉｇｈ，ａｎｄｒｏｇｅｎ—ｒｅｇｕｌａｔｅｄ　ａｃｔｉｖｉｔｙ　ｏｆ　ｈｅ　ｔｐｒｏｓｔａｔｅ．ｓｐｅｃｉｆｉｃ　ａｎｔｉｇｅｎ　ｐｒｏｍｏｔｅｒ．Ｍｏｌ　Ｅｎｄｏｃｒｉｎｏｌ　１９９７；　１１：１４８＿６１．　ｆｒｏｍ　ｍｉｔｏｃｈｏｎｄｒｉａ　ｂｌｏｃｋｅｄ．Ｓｃｉｅｎｃｅ　１９９７；２７５：ｌｌ２９－３２．　２　１　Ｊｕｒｇｅｎｓｍｅｉｅｒ　ＪＭ，Ｘｉｅ　Ｚ，Ｄｅｖｅｒａｕｘ　Ｑ，Ｅｌｌｅｒｂｙ　Ｌ，Ｂｒｅｄｅｓｅｎ　Ｄ，　Ｒｅｅｄ　ＪＣ．Ｂａｘ　ｄｉｒｅｃｔｌｙ　ｉｎｄｕｃｅｓ　ｒｅｌｅａｓｅ　ｏｆ　ｃｙｔｏｃｈｒｏｍｅ　ｃ　ｆｒｏｍ　ｉｓｏｌａｔｅｄ　ｍｉｔｏｃｈｏｎｄｒｉａ．Ｐｒｏｃ　Ｎａｔｌ　Ａｃａｄ　Ｓｃｉ　ＵＳＡ　１９９８；９５：　３１　ＣｌｅｕＯｅｎｓＫ，ＶａｎＥＣ，ＶａｎｄｅｒＫＨ，ＢｒｉｎｋｍａｎＡＯ，Ｔｒａｐｍａｎ　Ｊ．　Ｔｗｏ　ｎｄｒｏｇｅｎ　ａｒｅｓｐｏｎｓｅ　ｒｅｇｉｏｎｓ　ｃｏｏｐｅｒａｔｅ　ｉｎ　ｓｔｅｒｏｉｄ　ｈｏｒｍｏｎｅ　ｒｅｇｕｌａｔｅｄ　ａｃｔｉｖｉｔｙ　ｏｆ　ｈｅ　ｐｒｏｓｔｔａｔｅ　ｓｐｅｃｉｉｆｃ　ａｎｔｉｇｅｎ　ｐｒｏｍｏｔｅｒ．Ｊ　４９９７－５００２．　２２　Ｈｕａｎｇ　Ｑ，Ｓｈｅｎ　ＨＭ，Ｓｈｕｉ　ＧＨ，Ｗｅｎｋ　ＭＲ，Ｏｎｇ　ＣＮ．Ｅｍｏｄｉｎ　ｉｎｈｉｂｉｔｓ　ｔｕｍｏｒ　ｃｅｌｌ　ａｄｈｅｓｉｏｎ　ｔｈｒｏｕｇｈ　ｄｉｓｒｕｐｔｉｏｎ　ｏｆ　ｔｈｅ　ｍｅｍ—　ｂｒｎａｅ　ｌｉｐｉｄ　ｒａｆｔ—ａｓｓｏｃｉａｔｅｄ　ｉｎｔｅｇｒｉｎ　ｓｉｇｎａｌｉｎｇ　ｐａｔｈｗａｙ．Ｃａｎｃｅｒ　Ｒｅｓ　２０ｏ６：６６：５８０７－１５．　２３　Ｆｕ　ＺＹ．Ｈａｎ　ＪＸ．Ｈｕａｎｇ　ＨＹ．Ｅｆｌｆｅｃｔｓ　ｏｆ　ｅｍｏｄｉｎ　ｏｎ　ｇｅｎｅ　ｅｘｐｒｅｓ—　ｓｉｏｎ　ｐｒｏｆｉｌｅ　ｉｎ　ｓｍａｌｌ　ｃｅｌｌ　ｌｕｎｇ　ｃａｎｃｅｒ　ＮＣＩ—Ｈ４４６　ｃｅｌｌｓ．Ｃｈｉｎ　Ｍｅｄ　Ｊ　２００７；１２０：１７１０—５．　２４　Ｚｅｇａｒｒａ—Ｍｏｒｏ　０Ｌ，Ｓｃｈｍｉｄｔ　ＬＪ，Ｈｕａｎｇ　Ｈ，Ｔｉｎｄａｌｌ　ＤＪ．Ｄｉｓｒｕｐ—　ｔｉｏｎ　ｏｆ　ａｎｄｒｏｇｅｎ　ｒｅｃｅｐｔｏｒ　ｆｕｎｃｔｉｏｎ　ｉｎｈｉｂｉｔｓ　ｐｒｏｌｉｆｅｒａｔｉｏｎ　ｏｆ　ｎａｄｒｏｇｅｎ—ｒｅｆｒａｃｔｏｒｙ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌｓ．Ｃａｎｃｅｒ　Ｒｅｓ　２００２；　６２：１００８－１３．　２５　Ｍｉｔｃｈｅｌｌ　ＳＨ．Ｚｈｕ　Ｗ　Ｙｏｕｎｇ　ＣＹ　Ｒｅｓｖｅｒａｔｒｏｌｉｎｈｉｂｉｔｓ　ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ａｎｄ　ｆｕｎｃｔｉｏｎ　ｏｆ　ｔｈｅ　ａｎｄｒｏｇｅｎ　ｒｅｃｅｐｔｏｒ　ｉｎ　ＬＮＣａＰ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌｓ．Ｃａｎｃｅｒ　Ｒｅｓ　１９９９；５９：５８９２－５．　２６　Ｘｉｎｇ　Ｎ，Ｃｈｅｎ　Ｙ　Ｍｉｔｃｈｅｌｌ　ＳＨ，Ｙｏｕｎｇ　ＣＹ　Ｑｕｅｒｃｅｔｉｎ　ｉｎｈｉｂｉｔｓ　ｈｔｅ　ｅｘｐｒｅｓｓｉｏｎ　ｎａｄ　ｆｕｎｃｔｉｏｎ　ｏｆｔｈｅ　ａｎｄｒｏｇｅｎ　ｒｅｃｅｐｔｏｒ　ｉｎ　ＬＮＣａＰ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌｓ．Ｃａｒｃｉｎｏｇｅｎｅｓｉｓ　２００１：２２：４Ｏ９Ｌ—ｌ４．　２７　ＨｅＭ＿Ｌ，ＹｕａｎＨＱ，ＪｉｎａｇＡＬ，ＧｏｎｇＡＹ，Ｃｈｅｎｗｗ，ＺｈａｎｇＰＪ，　ａ１．Ｇｕｍ　ｍａｓｔｉｃ　ｉｎｈｉｂｉｔｓ　ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ａｎｄ　ｆｕｎｃｔｉｏｎ　ｏｆ　ｈｔｅ　ａｎｄｒｏｇｅｎ　ｒｅｃｅｐｔｏｒ　ｉｎ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌｓ．Ｃａｎｃｅｒ　２００６；ｌ０６：　２５４７－５５．　２８　Ｂｉｎａｃｏｌｅｌｌａ　Ｍ，Ｖａｌｅｎｔｉｎｉ　Ａ，Ｍｉｎｅｌｌａ　Ｄ，Ｖｅｃｃｈｉｏｎｅ　Ｌ，Ｄ’Ａｍｉｃｏ　Ｃｈｉｌｌｅｍｉ　Ｇ．ｅｔ　ａ１．Ｅｆｆ＆ｔｓ　ｏｆｄｕｔａｓｔｅｒｉｄｅ　ｏｎ　ｔｈｅ　ｅｘｐｒｅｓｓｉｏｎ　ｏｆｇｅｎｅｓ　ｒｅｌａｔｅｄ　ｔｏ　ｎａｄｒｏｇｅｎ　ｍｅｔａｂｏｌｉｓｍ　ｎａｄ　ｒｅｌａｔｅｄ　Ｄａｔｈｗａｙ　ｉｎ　ｈｕｍａｎ　ｐｒｏｓｔａｔｅ　ｃａｎｃｅｒ　ｃｅｌｌ　ｉｆｎｅｓ．Ｉｎｖｅｓｔ　Ｎｅｗ　Ｄｒｕｇｓ　２００７：２５：４９　１＿７．　２９　Ｖｌａｌｅｎｔｉｎｉ　Ａ，Ｂｉａｎｃｏｌｅｌｌａ　Ｍ，Ａｍａｔｉ　Ｆ，Ｇｒａｖｉｎａ　Ｐ＇Ｍｉａｎｏ　Ｒ，　－６３４．　Ｂｉｏｌ　Ｃｈｅｍ　１９９６；２７１：６３７９－８８．　３２　Ｃｈｅｎ　Ｘ，Ｂａｒｑｏｎｅｔｔｉ　Ｊ，Ｐｒｉｖｅｓ　Ｃ．ｐ５３，ｔｈｒｏｕｇｈ　ｐ２　１（ＷＡＦ１，　ＣＩＰ１），ｉｎｄｕｃｅｓ　ｃｙｃｌｉｎ　Ｄ１　ｓｙｎｔｈｅｓｉｓ．Ｃａｎｃｅｒ　Ｒｅｓ　１９９５；５５：　４２５７＿６３．　３３　Ｃｏｌｍａｎ　ＭＳ．Ａｆｓｈａｒｉ　ＣＡ．Ｂａｒｒｅｔｔ　ＪＣ．Ｒｅｇｕｌａｔｉｏｎ　ｏｆ　ｐ５３　ｓｔａ—　ｂｉｌｉｔｙ　ａｎｄ　ａｃｔｉｖｉｔｙ　ｉｎ　ｒｅｓｐｏｎｓｅ　ｔｏ　ｇｅｎｏｔｏｘｉｃ　ｓｇｅｓｓ．Ｍｕｔａｔ　Ｒｅｓ　２０００：４６２：１７９—８８．　３４　Ｗｉｎｔｅｒｓ　ＺＥ．Ｐ５３　ｐａｔｈｗａｙｓ　ｉｎｖｏｌｖｉｎｇ　Ｇ２　ｃｈｅｃｋｐｏｉｎｔ　ｒｅｇｕｌａ—　ｔｏｒｓ　ｎａｄ　ｈｔｅ　ｒｏｌｅ　ｏｆｔｈｅｉｒ　ｓｕｂｃｅｌｌｕｌａｒ　ｌｏｃａｌｉｚａｔｉｏｎ．Ｊ　Ｒ　Ｃｏｌｌ　Ｓｕｒｇ　Ｅｄｉｎｂ　２００２；４７：５９　１－８．　３５　Ｇｒｅｅｎ　ＤＲ．Ｂｉｓｓｏｎｎｅｔｔｅ　ＲＰ，Ｃｏｔｔｅｒ　ＴＧ．Ａｐｏｐｔｏｓｉｓ　ａｎｄ　ｃａｎｃｅｒ．　Ｉｍｐｏｒｔａｎｔ　Ａｄｖ　Ｏｎｃｏｌ　１９９４；ｌ１：３７－５２．　３６　Ｈｓｕ　ＳＬ，Ｙｉｎ　ＳＣ，Ｌｉｕ　ＭＣ，Ｒｅｉｃｈｅｒｔ　Ｕ，ＨｏⅥ　．Ｉｎｖｏｌｖｅｍｅｎｔ　ｏｆ　ｃｙｃｌｉｎ—ｄｅｐｅｎｄｅｎｔ　ｋｉｎａｓｅ　ａｃｔｉｖｉｔｉｅｓ　ｉｎ　ＣＤ４３７一ｉｎｄｕｃｅｄ　ａｐｏｐｔｏｓｉｓ．Ｅｘｐ　Ｃｅｌｌ　Ｒｅｓ　１９９９；２５２：３３２－４１．　３７　Ｋｒｏｅｍｅｒ　Ｇ．Ｔｈｅ　ｐｒｏｔｏ—ｏｎｃｏｇｅｎｅ　Ｂｃｌ一２　ａｎｄ　ｉｔｓ　ｒｏｌｅ　ｉｎ　ｒｅｇｕｌａｔ—　ｉｎｇ　ａｐｏｐｔｏｓｉｓ．Ｎａｔ　Ｍｅｄ　１９９７；３：６１４—２０．　３８　Ｓｔｒｏｂｅｌ　Ｔ，Ｓｗａｎｓｏｎ　Ｌ，Ｋｏｒｓｍｅｙｅｒ　Ｓ，Ｃａｎｎｉｓｔｒａ　ＳＡ．Ｂａｘ　ｅｎｈａｎｃｅｓ　ｐａｃｌｉｔａｘｅｌ・・ｉｎｄｕｃｅｄ　ａｐｏｐｔｏｓｉｓ　ｔｈｒｏｕｇｈ　ａ　ｐ５３・－ｉｎｄｅ・－　ｐｅｎｄｅｎｔ　ｐａｔｈｗａｙ．Ｐｒｏｃ　Ｎａｔｌ　Ａｃａｄ　Ｓｃｉ　ＵＳＡ　１９９６；９３：１４Ｏ９４—　９．　３９　Ｈｕａｎｇ　Ｊ，ｗｕｕ，Ｔａｓｈｉｏｒ　Ｓ，Ｏｎｏｄｅｒａ　Ｓ，ＩｋｅｊｉｍａＴ　Ｂｃｌ一２　ｕｐ—　ｒｅｇｕｌａｔｉｏｎ　ａｎｄ　Ｐ—ｐ５３　ｄｏｗｎ—ｒｅｇｕｌａｔｉｏｎ　ａｃｃｏｕｎｔ　ｆｏｒ　ｔｈｅ　ｌｏｗ　ｓｅｎｓｉｔｉｖｉｔｙ　ｏｆ　ｍｕｒｉｎｅ　Ｌ９２９　ｆｉｂｒｏｓａｒｃｏｍａ　ｃｅｌｌｓ　ｔｏ　ｏｒｉｄｏｎｉｎ—　ｉｎｄｕｃｅｄ　ａｐｏｐｔｏｓｉｓ．Ｂｉｏｌ　Ｐｈａｒｍ　Ｂｕｌｌ　２００５：２８：２０６８－７４．　４０　Ｃｏｈｅｎ　ＧＭ．Ｃａｓｐａｓｅｓ：ｔｈｅ　ｅｘｅｃｕｔｉｏｎｅ￣ｏｆ　ａｐｏｐｔｏｓｉｓ．Ｂｉｏｃｈｅｍ　Ｊ　１９９７；３２６：１－１６．　Ｅｄｉｔｅｄ　ｂｙ　Ｄｒ　Ｒｏｂｅｒｔ　Ｈ．Ｇｅｔｚｅｎｂｅｒｇ　，，ｆｔｐ：／／ｗｗｗ，ａｓｉａａｎｄｒｏ．ｃｏｒｎ；ａｊａ＠￥１ｂ￥．８ｃ．ｃｎ