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.

Decoction of Chinese Herbal Medicine Fuzheng Kang‐Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl‐2/Caspase‐3 Pathway

“…Table 1 listed the components of this decoction and the FZKA decoction has been reported previously [ 10 ]. The batch to batch consistency studies (the chromatograms in FZKA decoction) using high-performance liquid chromatography (HPLC) analysis and chemical profiling of main constituents in FZKA decoction using ultra-high pressure liquid chromatography coupled with LTQ Orbitrap mass spectrometry have been reported previously [ 11 ]. All of the components from this prescription were soaked for 30 min before decoction.…”

“…Meanwhile, FZKA could enhance the disease control rate (DCR) as well as median survival time (MST) in NSCLC patients [ 9 , 10 ]. Mechanistically, we also found that FZKA inhibited growth of NSCLC cells through AMP-activated protein kinase alpha- (AMPK α -) mediated induction and interplay of insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a), demonstrating definite therapeutic effect in lung cancer [ 11 ]. More recently, we have observed that FZKA decoction inhibits the growth of NSCLC cells through phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (Akt)-mediated inhibition of Nuclear factor- κ B (NF- κ B) subunit p65, followed by reducing expression of cell surface-associated mucin-1 (MUC1).…”

Traditional Chinese medicine, Fuzheng Kang-Ai decoction, inhibits metastasis of lung cancer cells through the STAT3/MMP9 pathway

“…The present study was based on our previous clinical and fundamental findings, which indicated that FZKA could sensitize the effects of gefitinib on patients with late stage lung cancer, and prolong the PFS and MST in patients with NSCLC ( 17 – 20 ). In addition, FZKA was reported to inhibit lung cancer cell growth in vivo and in vitro ( 17 – 20 ). The present study aimed to determine the role and mechanisms of FZKA decoction on the process of lung cancer cell metastasis.…”

“…In addition, FZKA could enhance the disease control rate, and prolong the progression-free survival (PFS) and median survival time (MST) in patients with NSCLC ( 18 , 19 ). Furthermore, our recent study reported that FZKA inhibited lung cancer cell growth through AMP-activated protein kinase α-mediated induction, and an interplay between insulin-like growth factor-binding protein 1 and forkhead box O3a, indicating its therapeutic effect on lung cancer ( 20 ). Metastasis is the predominant cause of mortality in patients with lung cancer; however, the mechanism by which FZKA affects lung cancer metastasis remains to be elucidated.…”

Effects of Yangzheng Sanjie Decoction-containing serum mediated by microRNA-7 on cell proliferation and apoptosis in gastric cancer

“…YZSJD, the components of which were obtained from Kangmei Pharmaceutical Co., Ltd. (Guangdong, China) and identified by two pharmacological experts, was prepared as described by Ren et al ( 28 ). In order to establish the quality standards of the compounds of YZSJD, the preparation of crude extracts and subsequent high-performance liquid chromatography (HPLC) experiments were performed more than three times, as previously described ( 29 ).…”