Anti-tumor effect of 5-aza-2 %26apos;-deoxycytidine by inhibiting telomerase activity in hepatocellular carcinoma cells

作者：Tao Shuang Fen; Zhang Chang Song; Guo Xian Ling; Xu Yun; Zhang Shan Shan; Song Jian Rui; Li Rong; Wu Meng Chao; Wei Li Xin^*

来源：World Journal of Gastroenterology, 2012, 18(19): 2334-2343.

DOI：10.3748/wjg.v18.i19.2334

• 5-aza-2 %26apos
• -deoxycitidine
• Telomerase
• Hepatocellular carcinoma
• DNA methylation

AIM: To investigate the effect of the demethylating reagent 5-aza-2%26apos;-deoxycitidine (DAC) on telomerase activity in hepatocellular carcinoma (HCC) cell lines, SMMC-7721 and HepG2. %26lt;br%26gt;METHODS: The related gene expression in cell lines was examined by real-time reverse transcription-polymerase chain reaction and Western blotting analysis. The telomerase activity was examined by telomeric repeat amplification protocol-enzyme-linked immuno-sorbent assay and DNA methylation was determined by methylation-specific polymerase chain reaction. %26lt;br%26gt;RESULTS: The telomerase activity was significantly reduced in both cell lines treated with DAC, accompanied by downregulation of telomerase reverse transcriptase (hTERT). We also observed the effect of DAC on the methylation status of hTERT promoter and the expression of regulatory genes, such as c-myc, p15, p16, p21, E2F1, and WT1. The methylation status of hTERT promoter could be reversed in SMMC-7721 by DAC, but not in HepG2 cells. However, p16 expression could be reactivated by demethylation of its promoter, and c-Myc expression was repressed in both cell lines. Moreover, DAC could enhance the sensitivity to the chemotherapeutic agents, such as cisplatin, by induction of apoptosis of HCC cells. %26lt;br%26gt;CONCLUSION: The DAC exerts its anti-tumor effects in HCC cells by inhibiting the telomerase activity.

• 出版日期2012-5-21
• 单位中国人民解放军第二军医大学; 宿州学院; 苏州大学