genistein联合顺铂控制肝癌切除术后复发转移的实验研究

目的 研究genistein(三羟基异黄酮)增强顺铂对肝癌切除术后复发转移的抑制作用及其机制. 方法建立模拟人肝癌切除术后肿瘤高转移复发的裸鼠模型,分别给予genistein与顺铂腹腔注射,治疗4周后处死,观察裸鼠肝脏复发肿瘤大小和肺转移情况;用金氏公式计算q值研究两药的协同作用;免疫组化及实时荧光定量PCR检测肝脏复发肿瘤MMP-2蛋白及mRNA的表达.结果 gunistein与顺铂联用较单用组裸鼠肝脏肿瘤复发灶体积减小,肺转移数减少;genistein与顺铂联用在体内对裸鼠肝癌切除术后的复发肿瘤具有相加抑制作用,对肺转移具有协同抑制作用;免疫组化检测复发肿瘤MMP-2的蛋白表达,顺铂组比对照组表达增加(t=26.17、P＜0.05),genistein组和联用组表达比对照组降低(t=5.58,13.90,P＜0.05);实时荧光定量PCR检测genistein组MMP-2 mRNA表达是对照组的0.90倍,顺铂组是对照组的2.06倍,联合组是对照组的0.44倍.结论 genistein可增强顺铂防治肝癌切除术后肿瘤复发转移的化疗疗效;其机制可能与genistein能降低顺铂诱导的MMP-2表达增加有关.

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

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.