Chinese Herbal Medicine Fuzheng Kang-Ai Decoction Inhibited Lung Cancer Cell Growth through AMPKα-Mediated Induction and Interplay of IGFBP1 and FOXO3a.
Chinese Herbal Medicine Fuzheng Kang-Ai Decoction Inhibited Lung Cancer Cell Growth through AMPKα-Mediated Induction and Interplay of IGFBP1 and FOXO3a.
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中草药扶正抗艾汤通过 AMPKα 介导的诱导以及 IGFBP1 和 FOXO3a 的相互作用抑制肺癌细胞生长
DOI：
10.1155/2016/5060757
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Hann SS
中科院分区：
文献类型：
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作者：
Zheng F;Wu J;Li X;Tang Q;Yang L;Yang X;Wu W;Hann SS
本研究的目的是探讨中草药“扶正抗癌汤”（简称“FZKA”）抗非小细胞肺癌（NSCLC）的作用及其体外和体内机制。我们发现FZKA煎剂的作用显着抑制A549和PC9细胞的生长。此外，FZKA 增加 AMP 激活蛋白激酶 α (AMPKα) 的磷酸化，并诱导胰岛素样生长因子 (IGF) 结合蛋白 1 (IGFBP1) 和 O3a 型叉头同源盒 (FOXO3a) 的蛋白表达。 AMPKα 的特异性抑制剂（化合物 C）可阻断 FZKA 诱导的 IGFBP1 和 FOXO3a 蛋白表达。有趣的是，IGFBP1和FOXO3a的沉默克服了FZKA对细胞生长的抑制作用。此外，沉默IGFBP1减弱了FZKA煎剂对FOXO3a表达的影响，而外源FOXO3a的表达增强了FZKA刺激的AMPKα磷酸化。因此，FZKA 抑制异种移植裸鼠模型中的肿瘤生长。总的来说，我们的结果表明，FZKA 煎剂通过激活 AMPKα，然后诱导 IGFBP1 和 FOXO3a 蛋白来抑制 NSCLC 细胞的增殖。 FOXO3a 的外源表达反馈增强 FZKA 煎剂刺激的 IGFBP1 表达和 AMPKα 磷酸化。 IGFBP1 和 FOXO3a 的相互作用影响了 FAKA 汤剂的整体反应。
The aim of this study is to investigate the actions of Chinese herbal medicine, called “Fuzheng Kang-Ai” (FZKA for short) decoction, against non-small cell lung cancer (NSCLC) and its mechanisms in vitro and in vivo. We showed that the effect of FZKA decoction significantly inhibited growth of A549 and PC9 cells. Furthermore, FZKA increased phosphorylation of AMP-activated protein kinase alpha (AMPKα) and induced protein expression of insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a). The specific inhibitor of AMPKα (Compound C) blocked FZKA-induced protein expression of IGFBP1 and FOXO3a. Interestingly, silencing of IGFBP1 and FOXO3a overcame the inhibitory effect of FZKA on cell growth. Moreover, silencing of IGFBP1 attenuated the effect of FZKA decoction on FOXO3a expression, and exogenous expression of FOXO3a enhanced the FZKA-stimulated phosphorylation of AMPKα. Accordingly, FZKA inhibited the tumor growth in xenograft nude mice model. Collectively, our results show that FZKA decoction inhibits proliferation of NSCLC cells through activation of AMPKα, followed by induction of IGFBP1 and FOXO3a proteins. Exogenous expression of FOXO3a feedback enhances FZKA decoction-stimulated IGFBP1 expression and phosphorylation of AMPKα. The reciprocal interplay of IGFBP1 and FOXO3a contribute to the overall responses of FAKA decoction.