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

World J Gastroenterol. 2003 Jan;9(1):73-8. doi: 10.3748/wjg.v9.i1.73.

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 micromol/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.

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / metabolism
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • B7-1 Antigen / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / therapy
  • Cell Division
  • Cell Survival
  • Combined Modality Therapy
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy
  • Genetic Vectors*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Humans
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / therapy
  • Quercetin / metabolism
  • Quercetin / pharmacology*
  • Recombination, Genetic
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • B7-1 Antigen
  • Tumor Suppressor Protein p53
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Quercetin