【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)、Rho A和VEGF m RNA的表达;蛋白质印迹法(Western Blot)分别检测p21Ras、ERK2、I-κBα、NF-κB(p65)、HIF-1α和VEGF的蛋白水平。结果:洛伐他汀能使NF-κB(p65)、VEGF和RHo A m RNA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。更多还原

【Abstract】 Objective:To investigate the effects of lovastatin on Ras/NF-κB pathway in human highly metastatic ovarian carcinoma cell line(HO-8910PM). Methods:HO-8910 PM cells were treated with different concentrations of lovastatin for 48 h. The expression levels of Ras,NF-κB(p65),HIF-1α,and VEGF,Rho A m RNA were determined by reverse transcription-polymerase chain reaction(RT-PCR) assay. The levels of proteins Ras,ERK2,I-κB α,NF-κB(p65),HIF-1α,and VEGF were assessed by Western Blot analysis. Results:Lovastatin down-regulated the m RNA expression levels of NF-κB(p65),VEGF and RHo A m RNA,affected the distribution of proteins RAS,I-κB α,NF-κB(p65) in cytoplasm and membrane,and down-regulated the expression levels of proteins ERK2,HIF-1α,VEGF in HO-8910 PM 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.更多还原