The Effect Of Low-dose Of Cisplatin Combined Interferon-alpha On Anti-angiogenesis In Mice With H22 Hepatocellular

Objective To evaluate the anti-angiogenetic effect of the combination of continuous low-dose cisplatin(DDP)and interferon-α(IFN-α) in mice with H22 hepatocellular carcinoma,and investigate its anti-tumor effect and toxicity or adverse reaction.Methods Holland Kunming hepatocellular carcinoma mice were randomly divided into 4 groups(12 mice in each group):the low-dose Cisplatin(DDP) group,the interferon-α(IFN) group,the low-dose Cisplatin combined with interferon-α(DDP+IFN) group,and the control group.DDP(0.6mg/kg) was administered by intraperitoneal injection and/or IFN-α(2×10~4 IU) by subcutaneous injection once a day for two weeks. Mice in the control group were given equal amount of normal salt solution only.Then,the changes of tumor volume,body mass and toxicity or adverse reaction were observed.At the end of experiment,tumors were weighed after killed the mice.The tumor microvessel density(MVD),the expressions of vascular endothelial growth factor(VEGF) and matrix metaUoproteinase-2(MMP-2) were determined by immunohistochemistry.Results1.The changes of body mass and the toxicity or adverse reaction of the drugsDuring the experiment,the body masses in each group were increasing gradually. Compared with the drug groups,the body mass of mice in the control group increased more slowly in result of larger tumor load.One week after the administration,mice of the control group were losing appetite and fur shiny,moving slowly;mice in the drug groups had good appetite,color glossy and moved flexibly.And there were no significant differences between the DDP+IFN group and the DDP and IFN groups.2.The anti-tumor effectAfter the treatment,the tumor masses of mice in the drug groups were significantly lower than that in the control group(P＜0.05).The body masses of mice in the DDP group and IFN group had no significant difference(P＞0.05),and the rate of anti-tumor were 40.22%and 44.03%.Compared with the DDP group and IFN group,the body mass of mice in the DDP+IFN group was significantly lower(P＜0.05),and the rate of anti-tumor was 60.34%.3.The count of MVD and the expressions of VEGF and MMP-2Compared with the control group,the count of MVD and the expressions of VEGF and MMP-2 in each drug group were significantly lower(P＜0.05).There were no significant difference between the DDP group and IFN group(P＞0.05).The MVD count and the expression of VEGF and MMP-2 in the DDP+IFN group were lower than those in the DDP group and IFN group,and the difference was significant(P＜0.05).Conclusion In mice with H22 hepatocellular model,continuous low-dose cisplatin and interferon-αalone can inhibit angiogenesis,thus inhibiting the growth of tumors.The combination of low-dose DDP and IFN-αhas obvious synergetic action of anti-angiogenesis,it shows significant tumor inhibitory effect,with no more toxic and adverse reaction than treatment of DDP or IFN-αalone.The effect of anti-angiogenesis may be correlated with the decrease expression of VEGF and MMP-2 in the tumor.