Effect And Mechanism Of Metal Copper Complex In Human Hepatoma Cell Line SMMC-7721

Background and Objective:Hepatocellular carcinoma (of hepatocellular carcinoma, HCC), is one of the most common malignancy in the clinical global incidence is increasing year by year, more than626million people a year, living in malignant tumors,5; the annual death toll of nearly600,000, ranking3of tumor-related death[1]. Per100,000people in North America and some Western European countries, about10people suffering from liver cancer and lead to death[2], the incidence of hepatocellular carcinoma continues to increase rapidly in the United States, with rates increasing the fastest in white men45to54years of age. And some countries in Asia and Africa for every100,000people there will be50-150people have died. China is a high incidence of liver cancer, the incidence of about55%of the world, in the tumor-related death after lung cancer, the second highest. The clinical efficacy of chemotherapy drugs is not ideal, so look for high efficiency and low toxicity of anti-liver cancer drug is imminent.New metal copper complexes (N-Cu) is synthesized from inorganic Department of Chemistry, Zhengzhou University, it is anti-hypertension drug telmisartan ligand relative molecular mass of8copper together for8723g·mol-1macromolecular compounds. The existing experimental data show[3,4]N-Cu on S180and H22all have significant anti-tumor effect and less toxic, but their specific anti-tumor molecular mechanism is unclear. In this study, the new type metal copper complex (N-Cu) inhibit the in vitro proliferation of human hepatocellular carcinoma SMMC-7721cells and induce apoptosis, and to elucidate the possible mechanism of actions, anti-liver cancer drug to provide a theoretical basis for the further development of N-Cu. Methods:SMMC-7721cells were treated with different concentrations of N-Cu (0.3～24μmol·L-1). The inhibitory effect was examined by MTT assay. The cell cycle and apoptosis rates were determined by flow cytometry method (FCM). Daul fluorescent staining detect apoptotic morphology by acridine orange/ethidium bromide. The expression levels of Bcl-2, Bax and Caspase-3mRNA and protein were detected by RT-PCR and Western blot.Results:①N-Cu could remarkably inhibit the growth of SMMC-7721cells and induce, apoptosis, and the suppression was in time-and dose-response relationships. Cell cycle analysis revealed a decreased proportion of cells in G2/M and S phase, with arrest at G0/G1in this process.②With the increase of drug concentration, nuclear chromatin more and more of the orange cells, and there was condensation-shaped or cylindrical cells began to appear.③The expression levels of Bax and Caspase-3mRNA and protein were up-regulated, but inhibit the expression of Bcl-2mRNA and protein in the cells, and all the effects of N-Cu were in a dose-dependent manner. Conclusion:①N-Cu inhibits cell growth and induces apoptosis in SMMC-7721cells, which maybe related to the arrest of G0/G1phase.②The up-regulation of Bax and Caspase-3and down-regulation of the rate of Bcl-2/Bax, were looked upon as the most important mechanism of antitumor.②N-Cu is a potential anti-hepatoma effect of compounds.