茶多酚对小鼠Lewis肺癌移植瘤中NF-κB、COX-2、Survivin表达的影响

背景与目的 肺癌是全球第一大恶性肿瘤,前期研究表明茶多酚具有一定的抗肺癌新生血管生成作用,本研究旨在观察茶多酚对小鼠Lewis肺癌移植瘤中NF-κB、COX-2、Survivin表达的影响,进而探讨茶多酚抗新生血管生成的效应机制.方法 建立C57BL/6小鼠肺癌移植瘤模型,测定模型对照组、沙利度胺组、茶多酚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NF-κB、COX-2、Survivin表达水平,以探讨其抗肿瘤的分子机制.结果 实验表明,茶多酚具有如下作用:①沙利度胺组、茶多酚组以及茶多酚联合沙利度胺组的肿瘤抑制率分别为17.26％、20.81％和44.32％,茶多酚联合沙利度胺组与模型组瘤重比较,差异具有统计学意义(P＜0.05)；②NF-κB表达在茶多酚组及联合用药组有所降低,与模型对照组相比.联合用药组NF-κB表达明显下降,差异具有统计学意义( P＜0.05)；③COX-2表达在各治疗组均有所下降,与模型对照组相比,联合用药组表达明显下降(P＜0.05)；④Survivin表达在各治疗组均较模型对照组明显降低(p＜0.05),其中茶多酚组下降最为明显(P＜0.01).结论 茶多酚联合沙利度胺组对肺癌有明显抑制作用,其机制可能与抑制NF-κB信号通路的异常激活、抑制NF-κB活化、降低COX-2表达、并降低内皮细胞Survivin表达从而抗肺癌新生血管生成相关.

Effects of Tea Polyphenols on the Expression of NF-κB,COX-2 and Survivin in Lewis Lung Carcinoma Xenografts in C57BL/6 Mice

Background and objective Lung cancer is the leading cause of cancer-related deaths worldwide.The anti-angiogenic effect of tea polyphenols(TPs) on lung carcinoma was confirmed in our previous study.The effect of TPs on the expression of nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB),cyclooxygenase-2(COX-2),and Survivin in Lewis lung cancer xenograft in mice was observed to explore the anti-angiogenic mechanism of TPs.Methods Lewis lung carcinoma was successfully implanted in 32 C57BL/6 mice,which were then randomly divided into the model control group,the Thalidomide group,the TPs group and the TPs combined with Thalidomide group.The tumor inhibition rates in these groups were determined,whereas the expressions of NF-κB,COX-2 and Survivin were detected using immunohistochemical techniques to investigate the molecular mechanism of the anti-tumor effect of TPs.Results(1) The tumor inhibition rates in the Thalidomide control group,the TPs group and the TPs plus Thalidomide group were 17.26%,20.81%,44.32% respectively.Compared with the model control group,the tumor inhibition rate was significantly higher in the TPs plus Thalidomide group(P<0.05);(2) Compared with the model control group,the expression of NF-κB was significantly decreased in the TPs group and the TPs plus Thalidomide group,and it was significantly downregulated in the latter(P<0.05);(3) The expression of COX-2 decreased in all treatment groups,and was significantly downregulated in the TPs plus Thalidomide group compared with the model control group(P<0.05);(4) Compared with the model control group,Survivin expression was significantly downregulated in all treatment groups(P<0.05),and was most obviously reduced in the TPs plus the Thalidomide group(P<0.01).Conclusion TPs plus Thalidomide significantly inhibits Lewis lung cancer growth.TPs possibly downregulates the expression of NF-κB,COX-2 and Survivin in tumor tissue,thereby playing important roles in anti-angiogenesis.