Chinese Herbal Medicine Fuzheng Kang-Ai Decoction Inhibited Lung Cancer Cell Growth through AMPKα-Mediated Induction and Interplay of IGFBP1 and FOXO3a. (4th February 2016)

• Record Type: Journal Article
• Authors: Zheng, Fang; Wu, Jingjing; Li, Xiong; Tang, Qing; Yang, LiJun; Yang, Xiaobing; Wu, WanYin; Hann, Swei Sunny
• Other Names: Li Chun-Guang Academic Editor.
• Is Part Of: Evidence-based complementary and alternative medicine. Volume 2016(2016)
• Publication Date: 2016-02-04
• Subjects: Alternative medicine -- Periodicals; 615.505
• DOI: 10.1155/2016/5060757
• Languages: English
• ISSNs: 1741-427X

Abstract

Abstract : 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 (AMPK α ) and induced protein expression of insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a). The specific inhibitor of AMPK α (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 AMPK α . 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 AMPK α, followed by induction of IGFBP1 and FOXO3a proteins. Exogenous expression of FOXO3a feedback enhances FZKA decoction-stimulated IGFBP1 expression and phosphorylation of AMPK α . The reciprocal interplay of IGFBP1 and FOXO3a contribute to the overall responses of FAKA decoction.