洛伐他汀对人高转移卵巢癌HO-8910PM细胞Ras/NF-κB通路的影响

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-1α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-1α, 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-1α, 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-1α, 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.

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