文献类型：期刊文献

英文题名：Synergic effect of 3 '-azido-3 '-deoxythymidine and arsenic trioxide in suppressing hepatoma cells

作者：Chen, Che[1,2];Zhang, Yingmei[1];Wang, Yong[3];Huang, Dejun[1];Xi, Yaming[4];Qi, Yongmei[1]

第一作者：陈彻;Chen, Che

通信作者：Zhang, YM[1]

机构：[1]Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Gansu, Peoples R China;[2]Lanzhou Univ, Gansu Coll Tradit Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[3]Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China;[4]Lanzhou Univ, Hosp 1, Lanzhou 730000, Gansu, Peoples R China

第一机构：Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Gansu, Peoples R China.

年份：2011

卷号：22

期号：5

起止页码：435

外文期刊名：ANTI-CANCER DRUGS

收录：;Scopus(收录号：2-s2.0-79955054454);WOS:【SCI-EXPANDED(收录号:WOS:000289509400008)】；

基金：This study was supported by National Natural Science Foundation of China (No 30470320). The authors thank Dr Ron Moorhouse, Dr Weihong Ji, and Dr Yunlu Xu for their comments and English editing on the study.

语种：英文

外文关键词：arsenic trioxide; 3 '-azido-3 '-deoxythymidine; cancer treatment; caspase 3; oncology; telomerase

摘要：The aim of this study was to investigate the synergic antitumor effects of arsenic trioxide (As2O3) and 3'-azido-3'-deoxythymidine (AZT) on hepatoma cells and explore the possible molecular basis of these effects. These results showed that AZT enhanced the inhibitory effect of As2O3 on HepG2 and SMMC-7721 cell growth. The IC50 of As2O3 in combination with AZT was lower than that of As2O3 alone. A concentration-dependent synergic effect of As2O3 and AZT (CI < 1) was observed in all the tested combinations of these compounds. These results also showed that the combination of As2O3 and AZT dramatically and significantly increased the number of apoptotic cells in HepG2 and SMMC-7721 cells. Studies in vivo showed that the combination of As2O3 and AZT was statistically superior to either As2O3 or AZT alone in the treatment of tumor-bearing mice. As2O3 (1 mg/kg) containing AZT (50 mg/kg) inhibits proliferation of implanted hepatoma 22 by 56.35%. These results suggest that treating hepatoma with a combinination of As2O3 and AZT offers the advantages of reduced toxic side effects and improved therapeutic efficacy. To understand the mechanism through which As2O3 and AZT suppress tumors, we studied the effects of these compounds, both separately, and in combination, on telomerase and caspase-3 activity. The results showed that the growth inhibitory and apoptotic effects of As2O3 and AZT on human hepatoma cells could be related to the inhibition of telomerase and the activation of caspase 3. Anti-Cancer Drugs 22:435-443 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.