FoxM1抑制剂下调Rad51增敏顺铂对骨肉瘤耐药细胞的化疗抑制作用

发布时间：2018-05-20 16:29

  本文选题：骨肉瘤 + 化疗耐药　； 参考：《临床与实验病理学杂志》2017年04期

【摘要】：目的探讨FoxM1是否调控DNA修复基因Rad51参与顺铂(CDP)对骨肉瘤耐药细胞化疗抑制作用。方法采用逐步增加剂量间歇作用的方法诱导骨肉瘤耐药细胞系并分别命名为MG-63/R和HOS-MNNG/R。qRT-PCR、Western blot法检测耐药细胞与亲本细胞FoxM1和Rad51的mRNA及蛋白表达;耐药细胞中4μmol/L Thiostrepton处理后qRT-PCR、Western blot法检测FoxM1和Rad51的mRNA及蛋白表达。细胞计数法检测单独或联合运用4μmol/L Thiostrepton和2μg/m L CDP对骨肉瘤耐药细胞增殖率的影响。结果建立在2μg/mL CDP浓度中稳定生长的耐药细胞系MG-63/R和HOS-MNNG/R,耐药指数分别为30.52和37.87(均重度耐药)。FoxM1和Rad51的mRNA及蛋白水平在耐药细胞中表达较亲本细胞明显增高;在耐药细胞中联合运用4μmol/L Thiostrepton和2μg/mL CDP组较单独应用4μmol/L Thiostrepton组或2μg/mL CDP组细胞增殖率明显降低;耐药细胞4μmol/L Thiostrepton处理后FoxM1及Rad51的mRNA和蛋白表达均明显降低。结论 FoxM1及Rad51高表达可能参与骨肉瘤细胞对CDP耐药,FoxM1抑制剂Thiostrepton可能通过下调Rad51增强CDP对骨肉瘤耐药细胞的抑制作用。
[Abstract]:Objective to investigate whether FoxM1 regulates the role of DNA repair gene Rad51 in the inhibition of chemotherapeutic effects of cisplatin on drug-resistant osteosarcoma cells. Methods the drug-resistant osteosarcoma cell lines were induced by increasing the dose intermittently and named as MG-63/R and HOS-MNNGR / R.qRT-PCRN Western blot method respectively to detect the expression of mRNA and protein in FoxM1 and Rad51 of resistant and parental cells. After 4 渭 mol/L Thiostrepton treatment, the expression of mRNA and protein in FoxM1 and Rad51 were detected by qRT-PCR- Western blot. The effect of 4 渭 mol/L Thiostrepton and 2 渭 g / mL CDP alone or in combination on the proliferation of drug-resistant osteosarcoma cells was detected by cell counting method. Results the drug resistant cell lines MG-63/R and HOS-MNNGR, which grew stably at 2 渭 g/mL CDP concentration, had a drug resistance index of 30.52 and 37.87, respectively. The mRNA and protein levels of both severe drug resistant cells, FoxM1 and Rad51 were significantly higher than those of their parent cells. The proliferation rate of the cells treated with 4 渭 mol/L Thiostrepton and 2 渭 g/mL CDP was significantly lower than that of the 4 渭 mol/L Thiostrepton or 2 渭 g/mL CDP groups, and the mRNA and protein expressions of FoxM1 and Rad51 were significantly decreased after 4 渭 mol/L Thiostrepton treatment. Conclusion the high expression of FoxM1 and Rad51 may be involved in the inhibition effect of CDP on CDP resistant osteosarcoma cells by down-regulation of Rad51.
【作者单位】： 安徽医科大学基础医学院病理学教研室;安徽医科大学第一附属医院骨科;
【基金】：国家自然科学青年基金(81102041) 安徽省自然科学基金(11040606Q17)
【分类号】：R738.1

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