title: Chinese Herbal Medicine Fuzheng Kang-Ai Decoction Inhibited Lung Cancer Cell Growth through AMPKα-Mediated Induction and Interplay of IGFBP1 and FOXO3a.
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 (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.
authors.affiliation: Laboratory of Tumor Biology and Target Therapy, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Laboratory of Tumor Biology and Target Therapy, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Central Laboratory, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Tumor Biology and Target Therapy, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Laboratory of Tumor Biology and Target Therapy, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
authors.forename: LiJun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China; Higher Education Mega Center, No. 55, Neihuan West Road, Panyu District, Guangzhou, Guangdong Province 510006, China.
authors.forename: WanYin
authors.initials: W
authors.lastname: Wu
authors.affiliation: Laboratory of Tumor Biology and Target Therapy, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, Guangdong Province 510120, China; Higher Education Mega Center, No. 55, Neihuan West Road, Panyu District, Guangzhou, Guangdong Province 510006, China.
authors.forename: Swei Sunny
authors.identifier: 0000-0003-2030-5285
authors.initials: SS
authors.lastname: Hann