Ophiopogonin D inhibits proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating miR-519d-3p/EIF4E expression
- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 24
- DOI:
- 10.11569/wcjd.v27.i24.1473
- Key Word:
- 肝癌;麦冬皂苷D;miR-519d-3p;EIF4E;细胞增殖;迁移;侵袭
Abstract： 背景 麦冬皂苷D(ophiopogoninD,OPD)是中药麦冬提取物中重要的单体成分且具有抗癌作用,但是否具有抗肝细胞癌(hepatocellular carcinoma,HCC)作用还未知.本研究假设OPD能够通过上调miR-519d-3p表达进而下调真核细胞翻译起始因子4E(eukaryotic translation initiation factor 4E,EIF4E)表达发挥抗HCC作用.目的 探讨OPD对HCC细胞增殖、迁移和侵袭的影响及可能的作用机制.方法 培养HCC细胞HepG2和MHCC97,不同浓度(2.5 μmol/L、5 μmol/L、10tmol/L)的OPD作用48 h后,四甲基噻唑蓝染色法(methylthiazoletrazolium,MTT)检测细胞增殖,Transwell检测细胞迁移和侵袭,实时荧光定量PCR(real-time quantitative PCR,RT-qPCR)检测细胞中miR-519d-3p和EIF4E mRNA表达,Western blot 检测细胞周期蛋白Dl(CyclinD1)、p21、基质金属蛋白酶2(matrix metalloproteinase-2,MMP-2)、MMP-9和EIF4E蛋白表达,双荧光素酶报告基因实验验证miR-519d-3p和EIF4E之间关系.转染miR-519d-3pmimics、si-EIF4E构建miR-519d-3p过表达或EIF4E表达抑制的HepG2和MHCC97细胞,RT-qPCR检测细胞中miR-519d-3p表达或Western blot检测EIF4E蛋白表达验证转染效率.MTT、Transwell、Western blot分别检测过表达miR-519d-3p或抑制EIF4E表达对HepG2和MHCC97细胞增殖、迁移和侵袭,及CyclinD1、p21、MMP-2和MMP-9蛋白表达的影响.结果 与对照组比,OPD组HepG2细胞抑制率显著升高(P＜0.05),迁移和侵袭数显著降低(P＜0.05),HepG2细胞中CyclinD1、MMP-2和MMP-9蛋白表达显著降低(P＜0.05),p21蛋白表达显著升高(P＜0.05),miR-519d-3p表达显著升高(P＜0.05),EIF4E mRNA和蛋白表达显著降低(P＜0.05),且呈浓度依赖性.miR-519d-3p在HepG2细胞中靶向负调控EIF4E表达.miR-519d-3p过表达或抑制EIF4E表达均可抑制HepG2细胞增殖、迁移和侵袭.抑制miR-519d-3p表达部分逆转了OPD对HepG2细胞增殖、迁移和侵袭的抑制作用.结论 OPD可能通过调控miR-519d-3p/EIF4E表达抑制HCC细胞的增殖、迁移和侵袭.
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