title: Curcumin inhibited HGF-induced EMT and angiogenesis through regulating c-Met dependent PI3K/Akt/mTOR signaling pathways in lung cancer.
abstract: The epithelial-mesenchymal transition (EMT) and angiogenesis have emerged as two pivotal events in cancer progression. Curcumin has been extensively studied in preclinical models and clinical trials of cancer prevention due to its favorable toxicity profile. However, the possible involvement of curcumin in the EMT and angiogenesis in lung cancer remains unclear. This study found that curcumin inhibited hepatocyte growth factor (HGF)-induced migration and EMT-related morphological changes in A549 and PC-9 cells. Moreover, pretreatment with curcumin blocked HGF-induced c-Met phosphorylation and downstream activation of Akt, mTOR, and S6. These effects mimicked that of c-Met inhibitor SU11274 or PI3 kinase inhibitor LY294002 or mTOR inhibitor rapamycin treatment. c-Met gene overexpression analysis further demonstrated that curcumin suppressed lung cancer cell EMT by inhibiting c-Met/Akt/mTOR signaling pathways. In human umbilical vein endothelial cells (HUVECs), we found that curcumin also significantly inhibited PI3K/Akt/mTOR signaling and induced apoptosis and reduced migration and tube formation of HGF-treated HUVEC. Finally, in the experimental mouse model, we showed that curcumin inhibited HGF-stimulated tumor growth and induced an increase in E-cadherin expression and a decrease in vimentin, CD34, and vascular endothelial growth factor (VEGF) expression. Collectively, these findings indicated that curcumin could inhibit HGF-promoted EMT and angiogenesis by targeting c-Met and blocking PI3K/Akt/mTOR pathways.
authors.affiliation: Department of Respiratory Disease, The 117th hospital of PLA , Zhejiang, P.R. China.
authors.forename: Demin
authors.initials: D
authors.lastname: Jiao
authors.affiliation: Department of Respiratory Disease, The 117th hospital of PLA , Zhejiang, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, The 117th hospital of PLA , Zhejiang, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Respiratory Disease, The 117th hospital of PLA , Zhejiang, P.R. China.
authors.forename: Xiali
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Respiratory Disease, The 117th hospital of PLA , Zhejiang, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Respiratory Disease, The 117th hospital of PLA , Zhejiang, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Mou
authors.affiliation: Department of Respiratory Disease, The 117th hospital of PLA , Zhejiang, P.R. China.
authors.forename: Qing-Yong
authors.initials: QY
authors.lastname: Chen