Effects Of Gefitinib On Biological Behaviors Of Human Hepatoma Cell Line HepG2

Primary hepatocellular carcinoma has rather complication biological characters, with fast progress, high postoperative recurrence and poor prognosis. The keys to improving curative effects of present treatment methods for hepatocellular carcinoma are prevention of recurrence of hepatocellular carcinoma as well as correct choice of treating measures. The rapid development of molecular biology makes the biological therapy the fourth kind of treatment mode following prior three kinds of methods, ie, surgery, radiotherapy and chemotherapy. In the meantime, molecular targeting medicine is active and vigorous in clinical application.Gefitinib, an orally active small molecule EGFR tyrosine kinase inhibitor (EGFR-TKI) with inhibitory effects on the growth of a variety of tumors and tumor cells,which can induce blockage of cell cycle, increase cell apoptosis and decrease cell proliferation and has capacity of anti-vascularization and anti-metastasis. Gefitinib can also reverse the drug resistance and enhance the growth inhibiting effect of cytotoxic drugs.Recent studies indicate that Gefitinib can suppress the growth of different tumor cells,but the role in treatment of HCC is unclear.In this study,immunohistochemical stain method was used to detect the protein expression characteristics of EGFR osteopontin,ki-67in HepG2 cells to analyze its relation with hepatocarcinoma metastasis. Gefitinib was used to act on human hepatocellular carcinoma cell, with aiming to investigate the changes of HepG2 cells by means of MTT assay and apoptotic assay by flow cytometry. Explore the inhibitory effect of IRESSA on hepatocarcinoma metastasisObjective:To select inhibitor Gefitinib of EGFR TKI( tyrosine kinase receptor inhibitor) for treating HepG2 cells,and judge its effect on HepG2 cells.Methods :Effects of inhibitor of small molecule TKI Gefitinib on HepG2 cells .Cell inhibition ratio was detected by MTT and apoptosis by flow cytometry posterior to Gefitinib acting on HepG2 cells.Results:In human hepatocellular carcinoma cell strains like HepG2 cell, there could be seen strongly positive expression of EGFR, in which obvious cell growth inhibition was observed obviously, with apoptosis, decrease of cell density and obvious decrease of EGFR expression following management of Gefitinib.The expression of OPN and ki-67 is corrected with incasiveness and progression of HCC. The results of MTT detectd that relative inhibiting rate reached 50% when concentration of Gefitinib was 4μmol/L.The inhibiting rate increased with increase of drug concentration and acting time. After drug management, HepG2 cell apoptosis could be detected by flow cytometry. Cell apoptosis was correlated with concentration and acting time of the drug in dose-dependent and time- dependency.Conclusions:1 With different concentrations of Gefitinib treatment on HepG2 cells ,the expression of EGFR, OPN, ki-67 on HepG2 cells were significantly different, the protein expression decrease along with the drug concentration increased.The result demonstrated that Gefitinib inhibit the transfer of HepG2 cells and the role of the invasion in vitro.2 Gefitinib inhibition in vitro with a HepG2 cell growth and induced apoptosis of hepatocarcinoma cell. As the Gefitinib concentration increased, the inhibition of HepG2 cells and apoptosis increased. And this role have the time-dependent manner. Showed time-dependent and concentration-dependent dual characteristics.