Effect of genistein and cisplatin on recrrence and metastasis of hepatocellular cardnoma after curative resection in athymic mice

Abstract

Objective To study the inhibiting effect of genistein and cisplatin on tumor recurrence and metastasis after hepatectomy in mice. Methods A posthepatectomy high-metastatic-and-recurrent athymic mouse model simulating human HCC was established.Genistein,cisplatin,and combination genistein and cisplafin respectively were given intraperitoneally.Mice were sacrificed after 4 weeks,the volume and pulmonary metastasis of the recurrent tumor was observed.Caculate q value using Jin Zhengjun formula was used to evaluate the synergistic effect of combination genistein and cisplatin.Immunohistochemistry and real time fluorescent quantitation PCR were used to detect the expression of MMP2 and MMP-2 mRNA in liver recurrent tumor. Results Compared with single drug group,mice in genistein combined with cisplatin group had smaller liver recurrent focus volume,less pulmonary metastasis.Genistein and cisplatin displayed additional inhibiting effect on tumor recurrence and metastasis after hepatectomy in vivo,and displayed synergistic inhibiting effect on pulmonary metastasis.The MMP-2 expression of the recurrent tumor in single cisplatin group increased compared with control group(t=26.17、P＜0.05),while in single genistein group and genistein and cisplatin combined group it decreased(t=5.58,13.90,P＜0.05).The expression of MMP-2 mRNA in genistein group was 90%the level of the control group,in cisplatin group it was 2.06 times that of the control group,in combination genistein and cisplatin group it was 44%the level of the control group. Conclusions In vivo,genistein reinforces the effect of cisplatin in inhibiting tumor recurrence and metastasis after hepatectomy,possibly by a mechanism in which genistein inhibits the up-regulation of MMP-2 induced by cisplatin. Key words: Carcinoma,hepatocellular; Cisplatin; Neoplasm metastasis; Neoplasm recurrence,local:Genistein