雷公藤内酯醇逆转卵巢肿瘤微环境的体内实验研究

Reversal of Ovarian Tumor Microenvironment by Triptolide in Vivo

目的通过体内实验探究雷公藤内酯醇对SKOV3细胞成瘤裸鼠的作用机制。方法实验分组为:SKOV3组和SKOV3+雷公藤内酯醇组。ELISA检测各组血清IL-2、TNF-α、HIF-1α、CSF-1的含量,蛋白质免疫印迹及免疫组化检测肿瘤组织中VEGF-1、MMP-2的表达,观察瘤体大小、TUNEL检测各组肿瘤细胞凋亡情况。结果与SKOV3组相比,SKOV3+TP组裸鼠血清中的CSF-1和HIF-1α表达明显下降(P<0.05),而IL-2和TNF-α表达明显上升(P<0.05);与SKOV3组相比,SKOV3+TP组的细胞凋亡明显升高、肿瘤大小减小,免疫组化及蛋白质免疫印迹提示MMP-2及VEGF-1表达明显下降,差异具有统计学意义(P<0.05)。结论雷公藤内酯醇能显著抑制人上皮性卵巢癌细胞SKOV3的增殖,并诱导肿瘤细胞凋亡。雷公藤内酯醇作用于SKOV3细胞后,肿瘤微环境中的相关细胞因子及蛋白发生改变,从而影响肿瘤的生长,最终诱导肿瘤发生凋亡。

Objective To explore the mechanism of triptolide on SKOV3 tumor-forming nude mice by in vivo experiment.Methods The experiment was divided into SKOV3 group and SKOV3+triptolide group.The contents of IL-2,TNF,HIF-1αand CSF-1 in serum were detected by ELISA,the expressions of VEGF-1 and MPP-2 in tumor tissues were detected by western blot and immunohistochemistry,and tumor size and apoptosis of tumor cells were observed by TUNEL.Results Compared with SKOV3 group,the expressions of CSF-1 and HIF-1αin serum of SKOV3+TP group were significantly decreased(P<0.05),while the expressions of IL-2 and TNF-αwere significantly increased(P<0.05).Compared with SKOV3 group,cell apoptosis and tumor size were significantly increased in SKOV3+TP group,and the expression of MMP-2 and VEGF-1 was significantly decreased by immunohistochemistry and western blot,with statistical significance(P<0.05).Conclusion Triptolide can significantly inhibit the proliferation of human epithelial ovarian cancer cells SKOV3 and induce the apoptosis of tumor cells.After treating SKOV3 cells with triptolide,the related cytokines and proteins in the tumor microenvironment were changed,thus affecting the growth of tumor and eventually inducing tumor apoptosis.