Original Articles
Copyright ©The Author(s) 2001. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2001; 7(3): 345-351
Published online Jun 15, 2001. doi: 10.3748/wjg.v7.i3.345
Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice
Xing-Wang Wang, Jin-Hui Yuan, Ru-Gang Zhang, Li-Xia Guo, Yong Xie, Hong Xie
Xing-Wang Wang, Jin-Hui Yuan, Ru-Gang Zhang, Li-Xia Guo, Hong Xie, Department of Biotherapy, Shanghai Institute of Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
Yong Xie, Department of Biology, Hong Kong University of Science and Technology, China
Author contributions: All authors contributed equally to the work.
Supported by the National Postdoctoral Science Foundation of China, No. 199711.
Correspondence to: Professor Hong Xie, Department of Biotherapy, Shanghai Institute of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China. xiehong@sunm.shcnc.ac.cn
Telephone: +86-21-64315030 Fax: 0086-21-64331090
Received: November 13, 2000
Revised: November 24, 2000
Accepted: November 30, 2000
Published online: June 15, 2001
Abstract

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 vivo 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 heaptoma cells in vitro. In vivo, 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.

Keywords: alpha-fetoproteins/genetics; oligodeoxyribo nucleotides, antisense/pharmacology; liver neoplasms/pathology; tumor cells, cultured/drug effects; gene expression/drug effects