茶多酚对Lewis 肺癌小鼠移植瘤MMP-2、TIMP-2 表达的影响

目的:观察茶多酚对肺癌小鼠移植瘤基质金属蛋白酶-2(MMP-2)及其相应的组织金属蛋白酶抑制剂-2(TIMP-2)表达的影响,探讨茶多酚抗新生血管生成的效应机制。方法:建立57小鼠肺癌移植瘤模型,测定茶多酚低、高剂量组以及茶多酚联合沙利度胺组的肿瘤抑制率,并且采用免疫组化法检测各组MMP-2、TIMP-2表达水平以及MMP-2/TIMP-2比值,以探讨其抗肿瘤的分子机制。结果:实验表明,茶多酚有如下作用:①沙利度胺组、茶多酚低剂量组、茶多酚高剂量组、茶多酚低剂量联合沙利度胺组、茶多酚高剂量联合沙利度胺组的肿瘤抑制率分别为17.26%、16.94%、20.81%、21.94%和44.32%,茶多酚高剂量联合沙利度胺组与模型组瘤重比较,有统计学意义(P<0.05);②茶多酚各组及联合用药各组能下调肿瘤组织MMP-2蛋白表达,茶多酚高剂量联合沙利度胺组能上调TIMP-2蛋白表达,与模型对照组比较,均具有统计学意义(P<0.05);③用药各组MMP-2/TIMP-2比值均有所下降,茶多酚各组明显降低,茶多酚大剂量联合沙利度胺组比值下降最为显著。结论:茶多酚高剂量联合沙利度胺组对肺癌有明显抑制作用。其机制可能与下调MMP-2表达、上调TIMP-2表达、调整MMP-2/TIMP-2比值失衡状态,从而抗肺癌新生血管生成相关。

Effects of Tea Polyphenols on the Expression of MMP-2 and TIMP-2 in Lewis Lung Carcinoma Xenografted in C57BL/6 Mice

Objective: To observe the effect of Tea Polyphenols(TP) on the expression of matrix metalloproteinase-2(MMP-2) and its corresponding tissue inhibitor of metalloproteinase-2(TIMP-2) in Lewis lung cancer xenograft in mice,so as to explore TP’s anti-angiogenesis mechanism.Methods: Lewis lung carcinoma was successfully implanted in 48 C57BL/6 mice,which were then randomly divided into six groups namely model control group,Thalidomide control group,TP low-dose group,TP high-dose group,TP low-dose combined with Thalidomide group and TP high dose combined with Thalidomide group.Tumor inhibition rates of these groups were examined,while MMP-2 and TIMP-2 expression was detected applying immunohistochemical technique and MMP-2/TIMP-2 ratio was calculated,in order to investigate the molecular mechanism of TP’s anti-tumor effect.Results: According to our study,TP was proved to have the following effects:(1) The tumor inhibition rates of Thalidomide control group,TP low-dose group,TP high-dose group,TP low-dose plus Thalidomide group and TP high dose plus Thalidomide group were 17.26%,16.94%,20.81%,21.94%,44.32% respectively.Compared with model control group,the tumor inhibition rate rise in TP high dose plus Thalidomide group was of statistical difference(P<0.05).(2) Compared with model control group,the expression of MMP-2 was significantly down-regulated in all four groups containing TP(P<0.05),while TIMP-2 expression in TP high dose plus Thalidomide group was up-regulated(P<0.05).(3) The MMP-2/TIMP-2 ratio was reduced in every treatment group,and the ratio of TP high dose plus Thalidomide group was most obviously decreased.Conclusion: TP high dose plus Thalidomide can significantly inhibit Lewis lung cancer growth.And one of its possible mechanisms is to down-regulate MMP-2 expression,up-regulate TIMP-2 expression,reduce MMP-2/TIMP-2 ratio to normal range,thus play a important role in anti-angiogenesis process.