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 xenografts <i>in vivo</i>. Non-small cell lung carcinoma NCI-H1993 cells, which harbor a <i>MET</i> gene 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 xenografts <i>in vivo</i> by direct regulation of the MET signaling pathway. Theses antitumor effects were primarily a result of its anti-proliferation function.