Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice  

作　　者：Xing Wang Wang~1 Jin Hui Yuan~1 Ru Gang Zhang~1 Li Xia Guo~1 Yong Xie~2 Hong Xie~1 ~1Department of Biotherapy,Shanghai Institute of Cell Biology,Chinese Academy of Sciences,Shanghai 200031,China ~2Department of Biology,Hong Kong University of Science and Technology,ChinaDr.Xing Wang Wang earned Ph.D.from Shanghai Institute of Materia Medical,Chinese Academy of Sciences in 1997.Now a professor at Shanghai Institute of Cell Biology,Chinese Academy of Sciences. 

出　　处：《World Journal of Gastroenterology》2001年第3期345-351,共7页世界胃肠病学杂志（英文版）

基　　金：Supported by the National Postdoctoral Science Foundation of China,No.199711.

摘　　要：AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts. Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis. RESULTS: Antisense S-ODN treatment led to reduced AFP gene expression. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction. CONCLUSION: Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction.AIM To evaluate antihepatoma effect ofantisense phosphorothioate oligodeo-xyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nudemice.METHODS AFP gene expression was examinedby immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNson SMMC-7721 human hepatoma cell growth invitro was determined using microculturetetrazolium assay. In vivo antitumor activitiesof S-ODNs were monitored by measuring tumorweight differences in treated and control micebearing SMMC-7721 xenografts. Induction of cellapoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis.RESULTS Antisense S-ODN treatment led toreduced AFP gene expression. Specificantisense S-ODNs, but not control S-ODNs,inhibited the growth of heaptoma cells in vitro.In vivo. only antisense S-ODNs exhibitedobvious antitumor activities. FACS analysisrevealed that the growth inhibition by antisenseS. ODNs was associated with their cell apoptosisinduction.CONCLUSION Antisense S-ODNs targeted toAFP genes inhibit the growth of human hepatomacells and solid hepatoma, which is related totheir cell apoptosis induction.

关 键 词：Animals Apoptosis Carcinoma  Hepatocellular Gene Expression Gene Therapy Humans In Vitro Liver Neoplasms Male MICE Mice  Inbred BALB C Mice  Nude Neoplasm Transplantation Oligodeoxyribonucleotides  Antisense Research Support  Non-U.S. Gov't Transplantation  Heterologous Tumor Cells  Cultured ALPHA-FETOPROTEINS 

分 类 号：R735.7[医药卫生—肿瘤]