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首页> 外文期刊>Evidence-based complementary and alternative medicine: eCAM >Decoction of Chinese Herbal Medicine Fuzheng Kang-Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl-2/Caspase-3 Pathway
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Decoction of Chinese Herbal Medicine Fuzheng Kang-Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl-2/Caspase-3 Pathway

机译:中药扶正康艾汤通过STAT3 / Bcl-2 / Caspase-3途径诱导肺癌细胞凋亡

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Decoction of Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA for short) has been applied as adjuvant treatment strategy in advanced lung cancer patients for decades. We previously showed that FZKA decoction inhibited proliferation of non-small cell lung cancer (NSCLC) cells through activation of AMP-activated protein kinase alpha (AMPKα) signaling pathway, followed by inducing insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a) proteins, and enhanced the inhibition effect of gefitinib in lung cancer cell growth via inactivating PI3-K/Akt-mediated suppressing of cell surface-associated mucin-1 (MUC1) expression. In this study, we investigated the molecular mechanism by which FZKA decoction affected cell apoptosis in lung cancer cells. Our results show that FZKA induced apoptosis in lung cancer cells. Mechanistically, FZKA activated the caspase-3, PARP, and caspase-9 activities. Both antiapoptotic and proapoptotic proteins from Bcl-2 family were deregulated by FZKA exposure in lung cancer cells. In addition, FZKA reduced protein expressions of signal transducer and activator of transcription 3 (STAT3) and Jun activation domain-binding protein 1 (Jab1), while it concomitantly increased p21 protein. Moreover, the inhibitor of caspase-3 resisted the effect of FZKA on induction of apoptosis. Finally, exogenous overexpression of STAT3 overcame FZKA-inhibited protein expressions of Bcl-2 and myeloid cell leukemia-1 (Mcl-1) as well as Bax and blocked FZKA-induced activities of caspase-3 and caspase-9. Our results show that FZKA decoction promotes lung cancer cell apoptosis through STAT3/Bcl-2/caspase-3 signaling pathways. This study unveils potential novel molecular mechanism by which FZKA controls growth of human lung cancer cells.
机译:数十年来,中草药复方抗癌汤(简称FZKA)已被用作辅助治疗策略。我们以前表明FZKA汤可通过激活AMP激活的蛋白激酶α(AMPKα)信号通路来抑制非小细胞肺癌(NSCLC)细胞的增殖,然后诱导胰岛素样生长因子(IGF)结合蛋白1(IGFBP1 )和叉头同源盒型O3a(FOXO3a)蛋白,并通过灭活PI3-K / Akt介导的细胞表面相关粘蛋白1(MUC1)表达的抑制来增强吉非替尼对肺癌细胞生长的抑制作用。在这项研究中,我们研究了FZKA汤影​​响肺癌细胞凋亡的分子机制。我们的结果表明,FZKA诱导肺癌细胞凋亡。机械上,FZKA激活了caspase-3,PARP和caspase-9活性。来自Bcl-2家族的抗凋亡蛋白和促凋亡蛋白均通过FZKA暴露在肺癌细胞中失控。此外,FZKA减少了信号转导和转录激活子3(STAT3)和Jun激活结构域结合蛋白1(Jab1)的蛋白表达,而同时增加了p21蛋白。此外,caspase-3抑制剂可抵抗FZKA诱导细胞凋亡。最后,外源STAT3的过量表达克服了FZKA抑制的Bcl-2和骨髓细胞白血病1(Mcl-1)以及Bax的蛋白表达,并阻止了FZKA诱导的caspase-3和caspase-9的活性。我们的结果表明FZKA汤可通过STAT3 / Bcl-2 / caspase-3信号通路促进肺癌细胞凋亡。这项研究揭示了潜在的新颖分子机制,FZKA通过该机制控制人类肺癌细胞的生长。

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