Experimental Study On Antiproliferative Action Of Ginsenoside Rg3, Sorafenib, Oxaliplatin Joint Programs Toward Human Hepatoma Cell

Objective:In vitro studies of ginsenoside Rg3, sorafenib, oxaliplatin single agent and the joint impact on the growth of human hepatoma cell line, to find the best combinations and to explore its possible mechanism, in order to provide the basis for effective in the further animal experimental and clinical trials and ultimately to improve the clinical efficacy of the treatment of liver cancer.Methods:Different concentrations of ginsenoside Rg3, sorafenib, oxaliplatin single agent and the two drugs, three drugs combined effects of in vitro cultured human hepatoma cell line SMMC-7721, using different experimental methods to observe the cell lines the growth conditions:(1) Proliferation inhibition assay:MTT observe the effects of ginsenoside Rg3, sorafenib, oxaliplatin single agent and the two drugs, three drugs combination of SMMC-7721cell proliferation.(2) Through fluorescence-activated cell sorting observe the cell cycle distribution.(3) Immunofluorescence assay proliferation associated protein PCNA and CyclinD1.Results:(1) Ginsenoside Rg3, sorafenib, oxaliplatin monotherapy and the two drugs, three drugs significantly inhibited hepatoma SMMC-7721cell proliferation, the inhibition showing time and dose dependent; two-drug combination compared with single-agent show a better inhibitory effect and the three-drug combination compared with the two-drug combination also show a better inhibition effect;All groups showed additive or synergistic effect except few two drug groups with small dose concentrations show a antagonism effect.(2) By flow cytometry find ginsenoside Rg3arrested cells in G0/G1phase, sorafenib arrested cells in S phase, oxaliplatin arrested cells in S phase and G2/M phase. Combination therapy:ginsenoside Rg3plus oxaliplatin arrested cells in S phase and G2/M phase,sorafenib plus oxaliplatin arrested cells in S phase, ginsenoside Rg3plus sorafenib arrested cells in G2/M phase, ginsenoside Rg3plus sorafenib and oxaliplatin cells arrested cells in S phase and G2/M phase.(3) Immunization of them were fluorescence results showed that ginsenoside Rg3and oxaliplatin single agent compared with the control group express a significant difference (P<0.05), but sorafenib group compared with control group haven’t a significant difference; The two drugs and the three drugs combined each other show a significant difference (P<0.01) than the control group. Conclusion:Ginsenoside Rg3, sorafenib, oxaliplatin single agent and the two drugs, three drugs combination can effectively inhibit the proliferation of human hepatoma cell line SMMC-7721cells, and we found the two drugs group is better than the single group, three drugs group is better than two drugs group; Between differences groups of two drugs combination was not statistically significant. And cells were arrested in the corresponding period,the resistance lag effect is in the main role of oxaliplatin and sorafenib. The three drugs alone and the joint inhibit the proliferation of human hepatoma cell line SMMC-7721cells may closely related to reduce the express of protein PCNA and CylinD1.