吗啡通过激活ERK1/2信号通路促进胶质母细胞瘤细胞增殖

摘要

Objective To observe the effect of morphine on the proliferation of glioblastoma T98G and U118MG cells and to explore the possible mechanism. Methods Glioblastoma T98G and U118MG cells were cultured in plates for 24 h and randomly divided into five groups: control (con), morphine 0.1 μmol/L(M1),1.0 μmol/L (M2),10.0 μmol/L (M3) and 100.0 μmol/L (M4). MTS and BrdU methods were used to detect the prolifera-tion of glioblastoma T98G and U118MG cells-treated with morphine for 24 h and 48 h. Western blot analysis was applied for determing the level of p-ERK1/2 and cyclin D1 protein expression.Results Compared with the control group,morphine in M3 and M4 groups significantly promoted the proliferation of T98G and U118MG cells (P<0.05) in a concentration-and time-dependent manner. In addition,the level of ERK1/2 phosphorylation and cyclin D1 protein expression significantly increased in both M3 and M4 groups as compared with those of control group (P<0.05). Conclusions Morphine may promote the proliferation of glioblastoma T98G and U118MG cells through activating the ERK1/2 signaling pathway.%目的 观察吗啡对胶质母细胞瘤细胞系T98G和U118MG增殖的影响,并探讨其可能的作用机制.方法 将胶质母细胞瘤T98G、U118MG细胞接种于培养板培养24 h,随机分为对照组(con)、吗啡0.1 (M1)、1 (M2)、10 (M3)和100 μmol/L(M4)等5组.处理胶质母细胞瘤T98G和U118MG细胞24和48 h后,用甲臢MTS法和BrdU法检测细胞增殖;Western blot检测与瘤细胞增殖密切相关的磷酸化细胞外信号调节激酶1/2(p-ERK1/2)和细胞周期蛋白cyclin D1的蛋白表达.结果 与对照组比较,吗啡在M3、M4组显著促进T98G和U118MG细胞增殖(P<0.05),且呈浓度和时间依赖性;M3、M4组T98G、U118MG细胞内ERK1/2磷酸化水平和cyclin D1蛋白表达量均显著升高(P<0.05),且呈浓度和时间依赖性.结论 吗啡可能通过调节ERK1/2激活和cyclin D1蛋白表达水平促进胶质母细胞瘤T98G和U118MG细胞增殖.