Liver Cancer
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 15, 2003; 9(1): 65-68
Published online Jan 15, 2003. doi: 10.3748/wjg.v9.i1.65
Synergistic effect of cell differential agent-II and arsenic trioxide on induction of cell cycle arrest and apoptosis in hepatoma cells
Jian-Wei Liu, Yi Tang, Yan Shen, Xue-Yun Zhong
Jian-Wei Liu, Yi Tang, Yan Shen, Department of General Surgery, Cell Culture Laboratory, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, Guangdong Province, China
Xue-Yun Zhong, Department of Pathology, Jinan University Medical College, Guangzhou 510632, Guangdong Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Scientific Research Fund of Guangdong Province, No.1998110
Correspondence to: Dr. Jian-Wei Liu, Department of General Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220 Guangdong Province, China. mabeliu@public.guangzhou.gd.cn
Telephone: +86-20-84412233 Fax: +86-20-84429803
Received: June 3, 2002
Revised: June 23, 2002
Accepted: July 3, 2002
Published online: January 15, 2003
Abstract

AIM: To illustrate the possible role of cell differential agent-II (CDA-II) in the apoptosis of hepatoma cells induced by arsenic trioxide (As2O3).

METHODS: Hepatoma cell lines BEL-7402 and HepG2 were treated with As2O3 together with CDA-II. Cell surviving fraction was determined by MTT assay; morphological changes were observed by immunofluorescence staining of Hoechst 33258; and cell cycle and the apoptosis index were determined by flow cytometry (FCM).

RESULTS: Cytotoxity of CDA-II was low. Nevertheless, CDA-II could strongly potentiate arsenic trioxide-induced apoptosis. At 1.0 g/L CDA-II, IC50 of As2O3 in hepatoma cell lines was reduced from 5.0 µmol/L to 1.0 µmol/L (P < 0.01). The potentiation of apoptosis was dependent on the dosage of CDA-II. FCM indicated that in hepatoma, cell growth was inhibited by CDA-II at lower concentrations (< 2.0 g/L) primarily by arresting at S and G2 phase, and at higher concentrations (> 2.0 g/L) apoptotic cell and cell cycle arresting at G1 phase increased proportionally. The combination of two drugs led to much higher apoptotic rates, as compared with the either drug used alone.

CONCLUSION: CDA-II can strongly potentiate As2O3-induced apoptosis in hepatoma cells, and two drugs can produce a significant synergic effect.

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