Anti-tumor effect of 5-aza-2＇-deoxycytidine by inhibiting telomerase activity in hepatocellular carcinoma cells

AIM： To investigate the effect of the demethylating reagent 5-aza-2＇-deoxycitidine （DAC） on telomerase activity in hepatocellular carcinoma （HCC） cell lines, SMMC-7721 and HepG2. METHODS： The related gene expression in cell lines was examined by real-time reverse transcription-polymerase chain react...

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Bibliographic Details
Published in:World journal of gastroenterology : WJG 2012-05, Vol.18 (19), p.2334-2343
Main Authors: 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
Format: Article
Language:English
Subjects:
Antimetabolites, Antineoplastic - pharmacology
Azacitidine - analogs & derivatives
Azacitidine - pharmacology
Carcinoma, Hepatocellular - drug therapy
Cell Line, Tumor - drug effects
DNA Methylation - drug effects
Gene Expression - drug effects
HepG2细胞
Humans
Liver Neoplasms - drug therapy
Original
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Telomerase - antagonists & inhibitors
抗肿瘤作用
氮杂
甲基化试剂
端粒酶活性
端粒酶逆转录酶
肝癌细胞
酶联免疫吸附试验
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Summary:AIM： To investigate the effect of the demethylating reagent 5-aza-2＇-deoxycitidine （DAC） on telomerase activity in hepatocellular carcinoma （HCC） cell lines, SMMC-7721 and HepG2. 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 immunosorbent assay and DNA methylation was determined by methylation-specific polymerase chain reaction. RESULTS： The telomerase activity was significantly re-duced 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 expres- sion 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 chemothera- peutic agents, such as cisplatin, by induction of apoptosis of HCC cells. CONCLUSION： The DAC exerts its anti-tumor effects in HCC cells by inhibiting the telomerase activity.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v18.i19.2334