Chinese Herbal Medicine Fuzheng Kang-Ai Decoction Inhibited Lung Cancer Cell Gro through AMPKα-Mediated Induction and Interplay of IGFBP1 d FOXO3a

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 decoction significantly inhibited growth of A549 and I'C9 cells. Furthermore, FZKA increased phosphorylation of AM P activated protein kinase alpha (AMPKa) and induced protein expression of insulin -like growth factor (IGP) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOX03a). The specific inhibitor of AMP Ka (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 phosphorylation of AMPKa. 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 AMPKa, followed by induction of IGFBP1 and FOXO3a proteins. Exogenous expression of FOXO3a feedback enhances FZKA decoction -stimulated IGFBP1 expression and phosphorylation of AMPKa. The reciprocal interplay of IGFBP1 and FOX03a contribute to the overall responses of FAKA decoction.