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目的:研究MKP1对他莫昔芬耐药MCF7细胞耐药性的影响及其分子机制。方法:应用Real-time PCR和Western blot分析MKP1在MCF7和他莫昔芬耐药MCF7细胞中的表达变化;Western blot分析MKP1siRNA在他莫昔芬耐药MCF7细胞中对他莫昔芬诱导MAPK成员活化的影响;MTT比色法分析细胞活力;流式细胞仪分析细胞凋亡;SP600125抑制JNK活化。结果:与MCF7细胞相比,MKP1在他莫昔芬耐药MCF7细胞中表达上调;MKP1siRNA可增加他莫昔芬对耐药MCF7细胞活力的抑制作用;MKP1siRNA组与对照组相比,他莫昔芬介导的耐药MCF7细胞的凋亡显著增加;siRNA组与对照组相比,他莫昔芬诱导的JNK活化显著增强;SP600125抑制JNK活化后,MKP1siRNA组他莫昔芬耐药MCF7对他莫昔芬的耐药性部分恢复。结论:MKP1通过抑制他莫昔芬诱导的JNK活化维持MCF7他莫昔芬耐药细胞对他莫昔芬的耐药性。
Objective: To investigate the effect of MKP1 on the drug resistance of tamoxifen-resistant MCF7 cells and its molecular mechanism. Methods: The expression of MKP1 in MCF7 and tamoxifen-resistant MCF7 cells was analyzed by Real-time PCR and Western blot. Western blotting analysis of MKP1 siRNA induced tamoxifen-induced MAPK in tamoxifen-resistant MCF7 cells Activation; MTT colorimetric assay of cell viability; Flow cytometry analysis of apoptosis; SP600125 inhibition of JNK activation. Results: Compared with MCF7 cells, MKP1 was up-regulated in tamoxifen-resistant MCF7 cells. MKP1 siRNA increased the inhibitory effect of tamoxifen on the viability of MCF7 cells. In MKP1 siRNA group, compared with control group, The apoptosis of MCF7 cells induced by FEN was significantly increased. Compared with the control group, tamoxifen induced a significant increase of JNK activation. After SP600125 inhibited the activation of JNK, the expression of tamoxifen-resistant MCF7 in MKP1 siRNA group was significantly increased Drug resistance to moxifen partially recovered. Conclusion: MKP1 can maintain the resistance of tamoxifen-resistant MCF7 cells to tamoxifen by inhibiting tamoxifen-induced JNK activation.