The Effect Of Epirubici Combined With Nimotuzumab On Human Hepatocellular Carcinoma Cell Line HepG2

Backgroud & Objective: The epidermal growth factor receptor (EGFR ) is one kind growth factor receptor which has the tyrosine kinase activity, in normal cells its expression rate is low, but in variety of tumor cells such as lung cancer, colon cancer, kidney cancer, head and neck squamous cell carcinoma, etc, which expresses excessively. EGFR signal pathway plays an important role in cancer development. At present, more drugs about EGFR signal pathway have already been widely applied in cancer treatment. Reports in the literature, EGFR is high expression in tissue of liver cancer, and other tissue adjacent to which, to interfere EGFR signal pathway of hepatocellular carcinoma cell would affect cell growth is unclear. Nimotuzumab (h-R3) is a kind of human monoclonal antibodies which can recognize outside membrane structure domain of EGFR, and it is a new genetic engineering which can specially block EGFR mediated signal pathway. This study observed the influence of h-R3 and chemotherapy drug epirubici (EPI) alone or in combination on growth of human hepatocellular carcinoma cell line HepG2 cells.Methods:The experiment was initiated after human hepatocellular carcinoma cell line HepG2 cells subcultured 2-3d. MTT assay was performed to evaluated the growth inhibitory rate of HepG2 cells. Increasing dose of nimotuzumab and epirubici alone or in combination were administrated to HepG2 cells. The inhibitory effects of the drugs on cell proliferation at different time points were observed , and calculated q value when the two drugs combined. Different drug alone or combination effect on HepG2 cells apoptosis and cell cycle changes were determined by flow cytometry with PI staining.Results:Nimotuzumab and epirubici both inhibited the growth of HepG2 cells in a time- and dose-dependent manner. The single drug of nimotuzumab or epirubici had effect on HepG2 cells, after 72-hour treatment, the proliferation inhibition rate of HepG2 cells was (49.56±8.93)% and(92.97±1.19)%. Combination nimotuzumab and epirubici could increase the proliferation inhibition rate of HepG2 cells, which was(96.44±1.0)% after 72-hour treatment. And the two drugs had synergistic role on the proliferation inhibition by q value. From flow cytometry result, after the drug nimotuzumab and epirubici alone or combined treatment, the apoptosis ratio of combination group was higher, and the apoptosis ratio was increased by treatment time prolonged. Nimotuzumab had effect on arresting the cells in G0/G1 phase while epirubici arresting the cells in s phase by cell cycle evaluated, which suggested the two drugs both could effect cell cycle changes of HepG2 cells.Conclusion:nimotuzumab combined with epirubici could enhance the therapeutic effects on HepG2 cells in vitro, which increased the sensitivity of HepG2 cells to epirubici. And both of the two drugs had effect on cell cycle changes of HepG2 cells.