摘要：
目的:研究洛伐他汀对人高转移卵巢癌HO-8910PM细胞Ras/NF-κB信号通路的影响.方法:不同浓度洛伐他汀分别作用HO-8910PM细胞48 h后,采用反转录聚合酶链式扩增反应(RT-PCR)分别检测Ras、HIF-1α、NF-κB(P65)、RhoA和VEGF mRNA的表达;蛋白质印迹法(Western Blot)分别检测p21Ras、ERK2、I-κBα、NF-κB(p65)、HIF-1 α和VEGF的蛋白水平.结果:洛伐他汀能使NF-κB(p65)、VEGF和RHoA mRNA表达水平下降,影响Ras蛋白在胞浆和胞膜之间的分布,下调HO-8910PM细胞的ERK2、HIF-1α、VEGF蛋白表达水平;还可以使胞浆中NF-κB(p65)上调、I-κBα下调,下调核内NF-κB(p65)水平和上调I-κBα.结论:洛伐他汀抗卵巢癌的分子机制主要干扰Ras蛋白在细胞膜上的锚定,抑制Ras/NF-κB信号通路密切相关.%Objective:To investigate the effects of lovastatin on Ras/NF-κB pathway in human highly metastatic ovarian carcinoma cell line (HO-8910PM).Methods:HO-8910PM cells were treated with different concentrations of lovastatin for 48 h.The expression levels of Ras,NF-κB (p65),HIF-1 α,and VEGF,RhoA mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR) assay.The levels of proteins Ras,ERK2,I-κB α,NF-κB (p65),HIF-1 α,and VEGF were assessed by Western Blot analysis.Results:Lovastatin down-regulated the mRNA expression levels of NF-κB (p65),VEGF and RHoA mRNA,affected the distribution of proteins RAS,I-κB α,NF-κB (p65) in cytoplasm and membrane,and downregulated the expression levels of proteins ERK2,HIF-1 α,VEGF in HO-8910PM cells.Conclusion:The molecular mechanisms of anti-ovarian cancer of lovastatin is closely associated with the interference of Ras anchoring cytomembrane and the inhibition of Ras/NF-κB pathway.
