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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。
Objective: To investigate the effect of lovastatin on Ras / NF-κB signaling pathway in human highly metastatic ovarian cancer cell line HO-8910PM. Methods: HO-8910PM cells were treated with Lovastatin at different concentrations for 48 h, respectively. The expressions of Ras, HIF-1α, NF-κB and Rho A were detected by reverse transcriptase-polymerase chain reaction (RT- And VEGF m RNA were detected by Western Blot. The protein levels of p21Ras, ERK2, I-κBα, NF-κB (p65), HIF-1α and VEGF were detected by Western Blot. RESULTS: Lovastatin decreased the expression of NF-κB (p65), VEGF and RHo A m RNA, and affected the distribution of Ras protein in the cytoplasm and membrane, down-regulated the expression of ERK2, HIF-1α, VEGF protein expression; also make cytoplasmic NF-κB (p65) upregulation of I-κBα downregulation of nuclear NF-κB (p65) levels and upregulation of I-κBα. Conclusion: The molecular mechanism of lovastatin anti-ovarian cancer mainly interferes with the anchoring of Ras protein on the cell membrane and the inhibition of Ras / NF-κB signaling pathway.