Liver Cancer
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 15, 2003; 9(1): 73-78
Published online Jan 15, 2003. doi: 10.3748/wjg.v9.i1.73
Synergetic anticancer effect of combined quercetin and recombinant adenoviral vector expressing human wild-type p53, GM-CSF and B7-1 genes on hepatocellular carcinoma cells in vitro
Ming Shi, Fu-Sheng Wang, Zu-Ze Wu
Ming Shi, Fu-Sheng Wang, Division of Biological Engineering, Institute of Infectious Disease, the 302 Hospital of PLA, Beijing 100039, China
Zu-Ze Wu, Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Fu-Sheng Wang, Division of Biological Engineering, Institute of Infectious Disease, the 302 Hospital of PLA, 26 Fengtai Lu, Beijing 100039, China. fswang@public.bat.net.cn
Telephone: +86-10-66933332 Fax: +86-10-63831870
Received: July 26, 2002
Revised: August 5, 2002
Accepted: August 16, 2002
Published online: January 15, 2003
Abstract

AIM: This study investigated the anti-cancer effect of combined quercetin and a recombinant adenovirus vector expressing the human p53, GM-CSF and B7-1 genes (designated BB-102) on human hepatocellular carcinoma (HCC) cell lines in vitro.

METHODS: The sensitivity of HCC cells to anticancer agents was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The viability of cells infected with BB-102 was determined by trypan blue exclusion. The expression levels of human wild-type p53, GM-CSF and B7-1 genes were determined by Western blot, enzyme-linked immunosorbent assay (ELISA) and flow cytometric analysis, respectively. The apoptosis of BB-102-infected or quercetin-treated HCC cells was detected by terminal deoxynucleotidyl transferase (TdT) assay or DNA ladder electrophoresis.

RESULTS: Quercetin was found to suppress proliferation of human HCC cell lines BEL-7402, HuH-7 and HLE, with peak suppression at 50 μmol/L quercetin. BB-102 infection was also found to significantly suppress proliferation of HCC cell lines. The apoptosis of BB-102-infected HCC cells was greater in HLE and HuH-7 cells than in BEL-7402 cells. Quercetin did not affect the expression of the three exogenous genes in BB-102-infected HCC cells (P > 0.05), but it was found to further decrease proliferation and promote apoptosis of BB-102-infected HCC cells.

CONCLUSION: BB-102 and quercetin synergetically suppress HCC cell proliferation and induce HCC cell apoptosis, suggesting a possible use as a combined anti-cancer agent.

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