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.
OBJECTIVE
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.


CONCLUSIONS
BB-102 and quercetin synergetically suppress HCC cell proliferation and induce HCC cell apoptosis, suggesting a possible use as a combined anti-cancer agent.
Shi
Ming
M
Division of Biological Engineering, Institute of Infectious Disease, the 302 Hospital of PLA, 26 Fengtai Lu, Beijing 100039, China.
Wang
Fu-Sheng
FS
Wu
Zu-Ze
ZZ
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D018122:B7-1 Antigen / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000628:therapy; D002455:Cell Division; D002470:Cell Survival; D003131:Combined Modality Therapy; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000628:therapy; D011794:Quercetin / Q000378:metabolism / Q000494:pharmacology*; D011995:Recombination, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D018122:B7-1 Antigen; D016159:Tumor Suppressor Protein p53; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011794:Quercetin