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薯蓣皂苷元通过调节DAXX亚细胞定位激活JNK/p38信号通路诱导MCF-7细胞凋亡

Diosgenin Induces Apoptosis of MCF-7 Cells by Regulating DAXX Subcellular Localization and Activating JNK/p38 Signaling Pathway

  • 摘要:
    目的 探讨薯蓣皂苷元对乳腺癌细胞增殖和凋亡的影响及潜在的分子机制。
    方法 以低、中、高剂量的薯蓣皂苷元作用于乳腺癌MCF-7细胞,MMT法检测细胞增殖力;流式细胞术检测细胞凋亡;核—浆蛋白分离法检测死亡结构域相关蛋白(DAXX)亚细胞定位;qRT-PCR和Western blot检测DAXX和c-Jun N末端激酶通路(JNK)相关蛋白表达水平。
    结果 薯蓣皂苷元可以显著抑制MCF-7细胞增殖、促进其凋亡,且呈现出一定的剂量依赖性;薯蓣皂苷元能够促进DAXX由细胞核进入细胞质,并且剂量依赖性地上调细胞表面死亡受体(Fas)表达,提高JNK和丝裂原活化蛋白激酶(p38)的磷酸化水平,激活JNK/p38信号通路。
    结论 薯蓣皂苷元抑制乳腺癌MCF-7细胞增殖并促进其凋亡,其作用机制可能与调节DAXX亚细胞定位、激活JNK/p38信号通路有关。

     

    Abstract:
    Objective To investigate the effect of diosgenin on the proliferation and apoptosis of breast cancer cells and its potential molecular mechanism.
    Methods The breast cancer cell line MCF-7 was treated with low, medium, and high doses of diosgenin, and cell proliferation was detected through the MMT method. Flow cytometry was used to detect cell apoptosis. Nuclear-cytoplasmic-protein separation method was applied to detect the subcellular localization of death associated protein (DAXX). qRT-PCR and Western blot were used to detect the expressions of DAXX and c-Jun N-terminal kinase pathway (JNK)-related proteins.
    Results Diosgenin considerably inhibited the proliferation of MCF-7 cells and promoted cell apoptosis in a concentration-dependent manner. Diosgenin can promote the movement of DAXX from nucleus into the cytoplasm. Diosgenin upregulated the expression of cell surface death receptor (Fas), increased the phosphorylation levels of JNK and mitogen activated protein kinase (p38), and activated the JNK/p38 signaling pathway with concentration dependence.
    Conclusion Diosgenin inhibits the proliferation and promotes the apoptosis of the breast cancer cell line MCF-7, whose mechanism may be related to the regulation of DAXX subcellular localization and the activation of JNK/p38 signaling pathway.

     

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