辛伐他汀对人高转移卵巢癌HO-8910PM细胞RasMAPKNF-κB通路的影响.pdfVIP

1398 实用医学杂志 2016 年第 32 卷第9 期 辛伐他汀对人高转移卵巢癌 HO-8910PM 细胞Ras/MAPK/NF- KB 通路的影响 符伟玉兰柳波李立吴科锋 摘要 目的;研究辛伐他汀(SIM) 对人高转移卵巢癌 HO-891OPM 细胞 Ras 信号通路的影响。方法:不同 浓度 SIM 分别作用 HO-891OPM 细胞 48 h 后，采用 RT-PCR 分别检测 Ras， HIF-lα、 NF-KB (P65) 、陆oA 和 VEGF mRNA 的表达，Westem blot 分别检测 Ras、 ERK2、 -KBα、 NF-KB (p65) 、 HIF-lα 和 VEGF 的蛋白水平， 于呼掺入法检测 MAPK 活性。结果:SIM 能使 NF-KB(p65) 、 VEGF 和 RHoA mRNA 表达降低，影响 R皿蛋白 在胞浆和胞膜间的分布，下调 ERK2、 HIF-lα、 VEGF 蛋白表达，并抑制活化的 NF-KB 往核内易位。结论:SIM 抗卵巢癌机制与抑制 Ras/MAPK 信号传导及其与 NF-KB 通~闸的交叉通讯密切相关。 关键词 辛伐他汀; 人高转移卵巢癌; HO-8910PM 细胞; Ras/NF-KB 通路 EtTect of simvastatin on cancer-翻sociated Ras/MAPKlNF -KB pathway in HO-8910PM ceU Iines FU Wei-知事 ， LAN Liu-bo , LI Li , WU Ke-feng. * Guan,gdong Medic a1 University , Zhanjiang 524023 , China Corresponding ωthor: WU Ke-feng E-mail: winokhere@ [Abstract 1 Obj眈tive To investigate the effects of simvastatin on Ras/NF-KB pathway in HO-8910PM cells. Methods HO-8910PM cells were cultured and treated with simvastatin in vitro. RT-PCR assay was used to detect the expressions of Ras , NF -KB (p65) , HIF-1α ， VEGF , RhoA mRNA. The levels of proteins Ras , ERK2 , I-KBα ， NF-KB(p65) ， HIF-lα ， VEGF were assessed by Westem blot.白le activity of MAPK was assayed by detecting the incorporation of [-y-32J ]A霄 to MAPK substrate peptide. Results Simvastatin down-regulated significantly the mRNA expressions of NF-KB(p65) ,VEGF and RHoA mRNA in HO-89 1OPM cells. Distributions of RAS , I-KBα ， NF -KB (p65) intracellular protein were also interrupted by simvastatin. The levels of proteins ERK2 , HIF-lα ， VEGF were down-regulated. Conclusion Antitumor mechanisms of simvastatin in HO- 8910PM cells may be assoc