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Therapeutic effect of AdCMVCD/5-FC system and metabolism of 5-FC in the treatment of human tongue squamous cell carcinoma

王安训 黄洪章 李苏

中华医学杂志(英文版)2003,Vol.116Issue(2):248-252,5.
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

王安训 1黄洪章 2李苏3

作者信息

  • 1. Department of Oral Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
  • 2. Department of Oral Maxillofacial Surgery, Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510120, China
  • 3. Cancer Center, Tumor Hospital, Sun Yat-Sen University, Guangzhou 510060, China
  • 折叠

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 chromatography

Key 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)

中华医学杂志(英文版)

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