The Experimental Study On Xiaoaiping Injection Alone And Its Relationship With Oxaliplatin And Endostar Combined With Anti-Hepatic Carcinoma Angiogenesis

Objective: Through the in vivo and in vitro experiment study Xiaoaiping(XAP) monotherapy and combined with Oxaliplatin and Recombinant human endostatin (Endostar) of angiogenesis in hepatocellular carcinoma and its mechanism. Providding the theory basis for the traditional Chinese medicine union chemotherapy and an anti-angiogenesis drugs pharmacological treatment primary liver cancer.Methods: (1) MTT assay was used to observe the different concentrations of XAP, Oxaliplatin, Endostar monotherapy or combination therapy on human umbilical vein endothelial cells (HUVEC) and human hepatoma celt SMMC-7721 proliferation. (2) Studying the Effects of different group therapy on CAM neovascularization.(3) Researching the Effects of the drugs on human hepatoma cell SMMC-7721 and human umbilical vein endothelial cells (HUVEC) in expression of angiogenesis-related factors,such as VEGF, MMP-2 and MMP-9 and so on.Results: (1) The monotherapy by XAP and Oxaliplatin could inhibit the proliferation of SMMC-7721 cells, and its inhibit proliferation in a time and concentration dependence. The two drugs and the three drugs group that XAP combined with Oxaliplatin and Endostar inhibited the proliferation of SMMC-7721 comparing with the single drug groups were different when the drugs had been given for 72hours (P<0.01). Endostar on the proliferation of SMMC-7721 inhibited compared with the control group shows no significant difference (P> 0.05).When 20μl/ml XAP Combined with 1μg/ml Oxaliplatin, the effects were additive. The 20μl/ml XAP and 6μg/ml Endostar United had a notable degree of drug synergism. (2) XAP can inhibit the proliferation of HUVEC, with time and dose dependence (P<0.01). Oxaliplatin also can inhibit the proliferation of HUVEC(P<0.01). When Endostar has been given for 72hours, in the range of 50～200ng/ml concentration, the performance on HUVEC proliferation was inhibited (P<0.01). The three drugs combination groups'effects is superior to other experimental groups (P<0.01), when the drugs was given 72hours. (3) 30μl/ml and 60μl/ml XAP,1μg/ml and 2μg/ml oxaliplatin, 6μg/ml Endostar monotherapy and combination of the two drugs can inhibit the chick embryo chorioallantoic membrane (CAM) angiogenesis, and we found that the experimental group and control group were significantly inhibited CAM angiogenesis (χ2=25.498, P<0.01). However, the differences among experimental groups were not statistically significant. (4) XAP, oxaliplatin, Endostar monotherapy and combination group can inhibite the expression of VEGF, MMP-2, MMP-9 on SMMC-7721 and HUVEC cells. Three drug treatments on SMMC-7721 cells, MMP-2, VEGF inhibition is superior to other experimental groups, the difference was significant (P<0.05), but its HUVEC cells the expression of MMP-2 inhibition excellent in the other groups, the difference was significant (P<0.05).Conclusion: XAP, oxaliplatin, Endostar single drug in vitro on the human liver cancer SMMC-7721 cell line and human umbilical vein endothelial cells (HUVEC) proliferation and in vivo angiogenesis in CAM has an inhibitory effect. XAP inhibited the proliferation of SMMC-7721 in a time and concentration dependence. Combination enhanced inhibition of SMMC-7721 and HUVEC proliferation. The mechanism may be inhibition of vascular endothelial cell tube formation and reduced cell VEGF, MMP-2 and MMP-9 expression, leading to Anti-angiogenesis of Primary liver cancer.