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Effect of preS2 antisense RNA on hepatocellular carcinoma with a novel delivery system

马春红 孙汶生 田培坤 王晓燕 刘素侠 张利宁 曹英林 朱法良 张秋

中华医学杂志(英文版)2003,Vol.116Issue(5):717-720,4.
中华医学杂志(英文版)2003,Vol.116Issue(5):717-720,4.

Effect of preS2 antisense RNA on hepatocellular carcinoma with a novel delivery system

Effect of preS2 antisense RNA on hepatocellular carcinoma with a novel delivery system

马春红 1孙汶生 1田培坤 2王晓燕 1刘素侠 1张利宁 1曹英林 1朱法良 1张秋1

作者信息

  • 1. Institute of Immunology, Medical College, Shandong University, Jinan 250012, China
  • 2. National Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai 200032, China
  • 折叠

摘要

Abstract

Objectives To construct a hepatoma directed gene delivery system which could transfer preS2 antisense RNA to liver cancer cells specifically, and to explore a new therapeutic strategy for hepatocellular carcinoma by blocking hepatitis B virus (HBV) with antisense RNA targeting hepatocellular carcinoma. Methods GE7 and HA20 were synthesized and mixed with pEBAF-as-preS2, a hepatocarcinoma specific HBV antisense expression vector, to construct a novel HBV antisense RNA delivery system named AFP-enhancing 4-element complex. Nude mice bearing hepatocelluar carcinoma cells HepG2.2.15 were injected with AFP-enhancing 4-element complex via a tail vein. Total RNA from tissues was extracted, and reversal transcription-ploymerase chain reaction (RT-PCR) was used to detect the expression of preS2. Different doses of AFP-enhancing 4-element complex was injected into nude mice at different time points, and tumor diameter was measured.Results AFP-enhancing 4-element complex was constructed successfully. RT-PCR showed preS2 antisense RNA delivered by AFP-enhancing 4-element complex only expressed in liver tumor HepG2.2.15 cells of the mice. After the treatment of AFP-enhancing 4-element complex with dose of 0.2 μg per mouse (once a week for 4 weeks), the mean tumor diameter of nude mice was significantly smaller than that of the control groups (0.995±0.35 cm vs 2.125±0.25 cm, P<0.01). Conclusions An HBV antisense RNA gene delivery system targeting hepatocellular carcinoma, AFP-enhancing 4-element complex, was constructed successfully. PreS2 antisense RNA expressed specifically in hepatocelluar carcinoma cells significantly inhibits tumor growth of mice bearing hepatocarcinoma HepG2.2.15 and may have therapeutic potential in HBV related hepatocarcinoma.

关键词

hepatitis B virus preS2 gene/antisense RNA/hepatocelluar carcinoma cell

Key words

hepatitis B virus preS2 gene/antisense RNA/hepatocelluar carcinoma cell

分类

医药卫生

引用本文复制引用

马春红,孙汶生,田培坤,王晓燕,刘素侠,张利宁,曹英林,朱法良,张秋..Effect of preS2 antisense RNA on hepatocellular carcinoma with a novel delivery system[J].中华医学杂志(英文版),2003,116(5):717-720,4.

基金项目

This study was supported by a grant from the National Natural Science Foundation of China (No. 39970333). (No. 39970333)

中华医学杂志(英文版)

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0366-6999

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