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, Zu-Ze Wu

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.

Figures

Figure 1
Figure 1
The suppressive effect of quercetin on the proliferation of BEL-7402, HLE and HuH-7 cell lines in vitro.
Figure 2
Figure 2
Proliferation inhibition of HCC cell lines transduced with BB-102.
Figure 3
Figure 3
The promotion of Que on HCC cell apoptosis induced by BB-102.
Figure 4
Figure 4
Effect of Que on the p53 expression in HCC cell lines transfered with BB-102. (lane1: control; lane2: with Que; lane3: with BB-102; lane4: with Que and BB-102).
Figure 5
Figure 5
Synergetic effect of BB-102 on quercetin suppression of growth of HCC cell lines.

Source: PubMed

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