Experimental study of combination therapy with ginsenoside Rg3, sorafenib and oxaliplatin versus mono-therapy on anti-angiogenic effect in hepatocelluar carcinoma

SUN Rong; GAO Shu; HUA Haiqing; YANG Aizhen; QIN Shukui

Abstract：Objective To observe the effect of ginsenoside Rg3,sorafenib, oxaliplatin alone or with different combination in neovascularization of tumor in nude mice with human hepatocellular carcinoma, and investigate the possible mechanisms. Methods Sixty nude mice with high metastatic human hepatocellular carcinoma transplanted in situ( LCI?D20) were randomly divided into gin?senoside Rg3 group(Group A), oxaliplatin group(Group B), sorafenib group(Group C), ginsenoside Rg3+ sorafenib group(Group D), ginsenoside Rg3+oxaliplatin group(Group E), oxaliplatin+sorafenib group(Group F), ginsenoside Rg3+ oxaliplatin+sorafenib group( Group G) and formal saline group( Group H) . The drug was administered eleven days later after the inoculation of tumor. The dosage of the medicine was as follows: ginsenoside Rg3(5mg/kg, qd, 14 days, intraperitoneal injection) and oxaliplatin(5mg/kg, q2d, 14 days, intraperitoneal injection) and sorafenib( 30mg/kg, qd, 14 days, gastric lavage) . All mice were sacrificed at 14 days af?ter administration, and tumor tissues were resected. Immunohistochemical method and Western blotting were used to detect the expres?sion rate and relative quantity of vascular endothelial growth factor( VEGF) , hypoxia?inducible factor( HIF)?1α, VEGF receptor( VEG?FR)?2 and micro?vessel density( MVD) in the tumor. Results The treatment groups presented different degrees of MVD lower than that of Group H( P<0?01) . Positive expression rates of VEGF in all treatment groups were decreased significantly compared with the Group H(P<0?05). Compared with Group H, positive expression rates of HIF?1α had a overall downward trend(P>0?05).The positive expression rates of VEGFR?2 in Group A, D and E were decreased significantly than that in Group H(P<0?05). Relative quantity of VEGF, HIF?1α and VEGFR?2 in Group A, B, C,D and E were decreased significantly than those in Group H( P<0?05) . Conclusion Ginsenoside Rg3 has an anti?angiogenic effect. Its anti?angiogenic effect might be related to the down?regulated expression of VEGF, HIF?1α and VEGFR?2. Ginsenoside Rg3 in combination with oxaliplatin or sorafenib can enhance the anti?angiogenic effect, but the expression of VEGF, HIF?1α and VEGFR?2 protein didn?t decreased significantly in the combination of three drugs. It shows that the antitumor effect of three drugs may still relate other mechanisms, which needed further study.