Liver Cancer
Copyright ©The Author(s) 2002. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 15, 2002; 8(5): 827-831
Published online Oct 15, 2002. doi: 10.3748/wjg.v8.i5.827
Telomerase inhibition and telomere loss in BEL-7404 human hepatoma cells treated with doxorubicin
Ru-Gang Zhang, Li-Xia Guo, Xing-Wang Wang, Hong Xie
Ru-Gang Zhang, Li-Xia Guo, Xing-Wang Wang, Hong Xie, Department of Biotherapy, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, the Chinese Academy of Sciences, Shanghai 200031, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Prof. Hong Xie, Department of Biotherapy, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, the Chinese Academy of Sciences, Shanghai 200031, China. xiehong@sunm.shcnc.ac.cn
Telephone: +86-21-64735609 Fax: +86-21-34010138
Received: February 28, 2002
Revised: July 1, 2002
Accepted: July 6, 2002
Published online: October 15, 2002
Abstract

AIM: To study the effects of doxorubicin on telomerase activity and telomere length in hepatocellular carcinoma.

METHODS: Telomerase activity was assayed with a non-radioisotopic quantitative telomerase repeat amplification protocal-based method. The effect of doxorubicin (DOX) on the growth of BEL-7404 human hepatoma cells was determined by microculture tetrazolium assay. Mean telomere length (terminal restriction fragment) was detected by Southern blot method. The expression of telomerase subunits genes was investigated by RT-PCR. Cell apoptosis and cell cycle distribution were evaluated by flow cytometry.

RESULTS: Telomerase activity was inhibited in a dose and time-dependent manner in BEL-7404 human hepatoma cells treated with DOX for 24, 48 or 72 h in concentrations from 0.156 to 2.5 μM which was crrelated with the inhibition of cell growth. No changes were found in the mRNA expression of three telomerase subunits (hTERT, hTR and TP1) after drug exposure for 72 h with indicated concentrations. The cells treated with DOX showed shortened mean telomere length and accumulated at the G2/M phase. However, there was almost no effects on cell apoptosis by DOX.

CONCLUSION: The telomerase inhibition and the telomere shortening by DOX may contribute to its efficiency in the treatment in hepatocellular carcinoma.

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