BIIB021对MDS细胞株Skm-1增殖的多靶点抑制作用研究

摘要

目的 探讨热休克蛋白90(HSP-90)抑制剂BIIB021对骨髓增生异常综合征(MDS)细胞株Skm-1增殖的多靶点抑制作用.方法 分别将0、100、200、400nmol/L BIIB021作用于4组Skm-1细胞(对照组、100 nmol/L组、200 nmol/L组、400 nmol/L组),培养24h后采用Western blot法检测各组细胞雷帕霉素靶蛋白(mTOR)、mTOR复合物1(mTORC1)、低氧诱导因子-1α(HIF-1α)蛋白表达水平.结果 各组Skm-1细胞mTOR蛋白表达水平比较差异无统计学意义(P＞0.05).各组Skm-1细胞mTORC1、HIF-1α蛋白表达水平比较差异均有统计学意义(均P＜0.05);组间两两比较差异亦均有统计学意义(均P＜0.05),即100nmol/L组、200 nmol/L组、400 nmol/L组Skm-1细胞mTORC1、HIF-1α蛋白表达水平均低于对照组,且400 nmol/L组表达水平最低.结论 BIIB021通过抑制mTORC1和HIF-1α蛋白的表达抑制Skm-1细胞增殖.%Objective To investigate the effect of HSP-90 inhibitor BIIB021 on the proliferation of myelodysplastic syndrome(MDS) Skm-1 cells and related mechanisms.Methods Skm-1 cells were treated with 100,200 and 400nmol/l BIIB021 for 24h.The expression of proteins mTOR,mTORC1,HIF-1α in Skm-1 cells was examined by Western blot.Results The expression of protein mTOR in Skm-1 cells was not significantly changed after treatment with different concentrations of BIIB021 (P ＞0.05).Compared to control group,the expression of mTORC1 and HIF-1α in Skm-1 cells treated with different concentrations of BIIB021 was significantly decreased (P＜0.05),and the expression was the lowest in the group of 400 nmol/L.Conclusion BIIB021 inhibits proliferation of MDS Skm-1 cells through down-regulating the expression of mTORC1 and HIF-1α.