益气解毒方联合盐霉素通过CD44/Ras信号通路调控鼻咽癌干细胞增殖、迁移和凋亡

Yi Qi Jie Du Formula and Salinomycin Combination Treatment Mediates Nasopharyngeal Carcinoma Stem Cell Proliferation, Migration and Apoptosis via CD44/Ras Signaling Pathway

    摘要
  • 摘要:
    目的研究益气解毒方（YQJDF）联合盐霉素（SAL）对鼻咽癌干细胞（NPC-SCs）的作用及其分子机制。
    方法采用细胞计数、CCK-8法、Transwell迁移实验、JC-1染色法分别观察联合用药对鼻咽癌干细胞增殖、迁移和凋亡的影响。Western blot法检测鼻咽癌干细胞蛋白表达水平。
    结果YQJDF联合SAL能协同抑制NPC-SC的增殖、迁移，诱导细胞凋亡。机制上，YQJDF联合SAL能协同上调凋亡蛋白cleaved Caspase-3、cleaved Caspase-7和cleaved Caspase-9的表达，协同降低CD44, p-c-Src, Ras, p-PKCδ, p-MEK, p-c-Raf, p-ERK1/2和p-AKT蛋白的表达。
    结论YQJDF与SAL联合应用具有抑制鼻咽癌干细胞增殖、迁移、诱导凋亡的协同作用，可能与CD44/Ras信号通路的下调密切相关。

     

    Abstract:
    ObjectiveTo assess the effects of Yi Qi Jie Du Formula (YQJDF) combined with salinomycin (SAL) on nasopharyngeal carcinoma stem cells (NPC-SCs) and investigate the underlying molecular mechanisms.
    MethodsCell counting methods, the CCK-8 assay, transwell migration assay and JC-1 staining, were used to observe the effects of the combination on the proliferation, migration and apoptosis of NPC stem cells, respectively. Western blot was used to detect the levels of protein in NPC-SCs.
    ResultsYQJDF combined with SAL had a synergistic effect on the inhibition of proliferation and migration and induction of NPC-SC apoptosis. Mechanistically, YQJDF combined with SAL synergistically upregulated the levels of apoptotic proteins, including cleaved Caspase-3, cleaved Caspase-7 and cleaved Caspase-9. Moreover, YQJDF combined with SAL synergistically decreased the levels of CD44, p-c-Src, Ras, p-PKCδ, p-MEK, p-c-Raf, p-ERK1/2 and p-AKT proteins.
    ConclusionsThe combination of YQJDF and SAL has a synergistic effect on the inhibition of NPC-SC proliferation and migration and induction of apoptosis, which may be closely related to the downregulation of the CD44/Ras signaling pathway.

     

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