Inhibitory Effect Of Recombinant Adenovirus H101 Combined With Sorafenib Against Hepatocellular Carcinoma In Vitro

Objective:To investigate the inhibitory effect of recombinant adenovirus HI01 combined with sorafenib on the proliferation and apopotosis of human hepatocellular carcinoma cell lines HepG2 and Hep3B in vitro, and discuss the possible mechanism.Methods:HepG2 and Hep3B cells were treated with HI01, sorafenib alone or in combination, with the untreated cells used as control. The proliferation inhibition effect was determined using CCK-8 assay. Apoptosis was analyzed by flow cytometry and 4,6-Diamidino-2-phenylindole (DAPI) staining. After treated with sorafenib, the sensitivity of HepG2 and Hep3B cell line to Ad-GFP were detected by flow cytometry. The expression of coxsackie-adenovirus receptor (CAR), extracellular regulated protein kinases (ERK), phosphorylated ERK (pERK) protein were detected by Western blot analysis.Results:Oncolytic adenovirus H101 and sorafenib used alone or together both inhibited the proliferation of HepG2 and Hep3B cells in a time-dose dependent manner and induced cell apopotosis. Compared with HI01 or sorafenib alone, co-treatment led to a stronger antitumor effect on HCC cells. Besides, it is showed that sorafenib could up-regulated the expression of CAR in HepG2 and Hep3B cells though inhibition of Raf/MEK/ERK signal transdution pathway and enhance the sensitivity of HepG2 and Hep3B cells to adenovirus.Conclusion:Oncolytic adenovirus HI01 and sorafenib used alone or together both inhibited the proliferation of HepG2 and Hep3B cells and induced cell apopotosis. Oncolytic adenovirus H101 and sorafenib show a synergistic effect at specific concentrations. And it's possible that sorafenib could enhance the sensitivity of HepG2 and Hep3B cells to adenovirus though up-regulation of the expression of CAR in cells, thus can be used to enhance the antitumor effect of oncolytic adenovirus.