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目的研究MEK/ERK通路阻断剂U0126对黑素瘤细胞A375增殖的影响,并探讨其作用机制。方法噻唑蓝法(MTT)测定U0126和传统抗癌药物达卡巴嗪(DTIC)分别及联合作用时对黑素瘤细胞A375的增殖抑制作用;流式细胞术检测不同药物处理组的细胞周期及凋亡情况;Western blot检测U0126处理后细胞p-ERK1/2的表达。结果药物作用24h时U0126单一用药组对细胞的增殖抑制率高于DTIC单一用药组(P<0.01);联合应用U0126和DTIC对细胞的增殖抑制率明显高于DTIC用药组(P<0.01);U0126组与对照组相比,G1期细胞比例数提高了21.83%(P<0.01),凋亡率提高了13.96%(P<0.01),联合用药组与对照组相比G1期比例增加了26.64%(P<0.01),凋亡率亦明显提高了25.20%(P<0.01);不同浓度U0126处理细胞后,细胞的p-ERK1/2均明显降低(P<0.01)。结论 MEK/ERK通路阻断剂U0126可显著抑制黑素瘤细胞的增殖,其机制可能与降低p-ERK1/2的表达从而参与细胞周期调控有关;联合U0126用药有望成为治疗黑素瘤新的有效途径。
Objective To investigate the effect of MEK / ERK pathway inhibitor U0126 on the proliferation of melanoma A375 cells and to explore its mechanism. Methods The inhibitory effect of U0126 and DTIC on the proliferation of melanoma A375 cells was detected by MTT assay. The cell cycle and apoptosis in different drug-treated groups were detected by flow cytometry The expression of p-ERK1 / 2 in U0126 cells was detected by Western blot. Results The inhibitory rate of U0126 single treatment group was higher than that of single DTIC treatment group (P <0.01) at 24 hours. The inhibition rate of U0126 and DTIC combined with UTIC treatment group was significantly higher than that of DTIC treatment group (P <0.01). Compared with the control group, the proportion of cells in G1 phase in U0126 group increased by 21.83% (P <0.01) and the apoptosis rate increased by 13.96% (P <0.01). Compared with the control group, the proportion of G1 phase increased 26.64 % (P <0.01), and the apoptosis rate was significantly increased by 25.20% (P <0.01). The expression of p-ERK1 / 2 in U0126 cells treated with different concentrations of U0126 significantly decreased (P <0.01). Conclusion MEK / ERK pathway inhibitor U0126 can significantly inhibit the proliferation of melanoma cells, and its mechanism may be related to decreasing the expression of p-ERK1 / 2 and participating in cell cycle regulation. Combined with U0126 is expected to become a new and effective treatment of melanoma way.