title: Antitumor activity of gambogic acid on NCI-H1993 xenografts via MET signaling pathway downregulation.
abstract: The present study aimed to investigate the anti-tumor mechanisms of gambogic acid (GA) on NCI-H1993 xenograftsin vivo. Non-small cell lung carcinoma NCI-H1993 cells, which harbor aMETgene amplification, were subcutaneously injected into athymic nude mice. The mice were randomly assigned to treatment with 10, 20 or 30 mg/kg GA for 3 weeks. At the end of the efficacy study, all the mice were sacrificed and the tumor tissues were subjected to western blot analysis and immunohistochemical (IHC) staining. GA inhibited NCI-H1993 xenograft tumor growth in a dose-dependent manner. Western blot analysis demonstrated that expression of phosphorylated (p)-MET and its downstream signaling molecules p-AKT and p-ERK1/2 were significantly inhibited by GA. IHC analysis of Ki-67 expression demonstrated that GA treatment resulted in dose-dependent inhibition of tumor cell proliferation. GA exerted antitumor effects on NCI-H1993 xenograftsin vivoby direct regulation of the MET signaling pathway. Theses antitumor effects were primarily a result of its anti-proliferation function.
authors.affiliation: Oncology Department, Baoding Second Central Hospital of Oncology, Zhuozhou, Hebei 072750, P.R. China.
authors.forename: Donglei
authors.initials: D
authors.lastname: Li
authors.affiliation: Oncology Department, Baoding Second Central Hospital of Oncology, Zhuozhou, Hebei 072750, P.R. China.
authors.forename: Huiwei
authors.initials: H
authors.lastname: Yang
authors.affiliation: Oncology Department, Baoding Second Central Hospital of Oncology, Zhuozhou, Hebei 072750, P.R. China.
authors.forename: Runpu
authors.initials: R
authors.lastname: Li
authors.affiliation: Oncology Department, Baoding Second Central Hospital of Oncology, Zhuozhou, Hebei 072750, P.R. China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Oncology Department, Baoding Second Central Hospital of Oncology, Zhuozhou, Hebei 072750, P.R. China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Wang
authors.affiliation: Oncology Department, Baoding Second Central Hospital of Oncology, Zhuozhou, Hebei 072750, P.R. China.
authors.forename: Dongjie
authors.initials: D
authors.lastname: Li
authors.affiliation: Oncology Department, Baoding Second Central Hospital of Oncology, Zhuozhou, Hebei 072750, P.R. China.
authors.forename: Shaolin
authors.initials: S
authors.lastname: Ma
authors.affiliation: Oncology Department, Baoding Second Central Hospital of Oncology, Zhuozhou, Hebei 072750, P.R. China.
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zhang
keywords: MET; NCI-H1993; gambogic acid; non-small cell lung cancer; receptor tyrosine kinase