首页|期刊导航|中华医学杂志(英文版)|Therapeutic effect of AdCMVCD/5-FC system and metabolism of 5-FC in the treatment of human tongue squamous cell carcinoma
中华医学杂志(英文版)2003,Vol.116Issue(2):248-252,5.
Therapeutic effect of AdCMVCD/5-FC system and metabolism of 5-FC in the treatment of human tongue squamous cell carcinoma
Therapeutic effect of AdCMVCD/5-FC system and metabolism of 5-FC in the treatment of human tongue squamous cell carcinoma
摘要
Abstract
Objective To investigate the therapeutic effect and metabolism of 5-fluorocytosine (5-FC ) in human tongue squamous carcinoma cells after treatment with adenovirus-medi ated cytosine deaminase (AdCMVCD)/5-FC system. Methods Human tongue squamous carcinoma cells (Tca8113 cell line) and its xenografts in BALB/c nude mice were treated with AdCMVCD/5-FC system. The killing effect in vitro and bystander effect were detected by microculture tetrazolium (MTT) assay . Tumor inhibition effect and histopathological changes were observed in vivo. High-performance liquid chromatography (HPLC) was performed to determine the metabolism of 5-FC in vitro and in vivo. Results AdCMVCD/5-FC system had strong killing effect and bystander effect on Tca8113 cells. Both condition media and cell extracts showed two peaks identified as 5- FC and 5-fluorouracil (5-FU) by HPLC and a time-dependent generation of 5-FU and concomitant time-dependent decreases of 5-FC. Compared to the control groups, mice treated with AdCMVCD/5-FC system demonstrated significant tumor regr ession (P<0.001); the tumor doubling time prolonged and inhibition rate was 92.62%. There were substantial tumor necrotic areas and infiltrative lymphocy tes around necrotic areas in the AdCMVCD/5-FC treated group under light microscope. There was a significantly low concentration of 5-FC and high concentratio n of 5-FU in tumor tissue, but only 5-FC was found in blood. Conclusion AdCMVCD/5-FC suicide gene system had significant in vitro and in vivo anti-tumor effect on human tongue squamous cell carcinomadue to convert 5-FC into 5-F U.关键词
suicide gene/cytosine deaminase/gene therapy/tongue tumor/carcinoma/high-performance liquid chromatographyKey words
suicide gene/cytosine deaminase/gene therapy/tongue tumor/carcinoma/high-performance liquid chromatography分类
医药卫生引用本文复制引用
王安训,黄洪章,李苏..Therapeutic effect of AdCMVCD/5-FC system and metabolism of 5-FC in the treatment of human tongue squamous cell carcinoma[J].中华医学杂志(英文版),2003,116(2):248-252,5.基金项目
This work was supported by a grant from "The 211 project" of Sun Yat-Sen University of Medical Sciences (No. 99074). (No. 99074)