P0063 Inhibition of STAT3 signalling and tumour cell growth in melanoma by atractylenolide II treatment

Abstract

Background Advanced melanoma accounts for most deaths from skin cancer. STAT3 (signal transducer and activator of transcription 3) has been reported to be constitutively activated in melanoma and contributes to tumour cell proliferation, survival, angiogenesis and metastasis, and immune evasion. Methods This study assessed inhibition of STAT3 signalling and tumour cell growth in melanoma by treatment with atractylenolide II (AT-II), a sesquiterpene isolated from the Chinese medicinal herb Atractylodis macrocephalae rhizoma (Baizhu in Chinese). Findings In this study we showed that AT-II dose-dependently and time-dependently inhibited cell proliferation and migration and induced apoptosis in both murine B16 and human A375 melanoma cells. AT-II significantly suppressed subcutaneous B16 xenograft tumour growth in mice and also potently and dose-dependently inhibited STAT3 and Src phosphorylation and activation in melanoma cells in vivo and in vitro. Results of cellular experiments also showed that AT-II lowered protein and mRNA expression of STAT3 target genes VEGF, MCL-1, Bcl-XL, MMP-2, MMP-9, and IL-10, which are involved in angiogenesis, cell apoptosis, invasion, and immune evasion, respectively. Additionally, STAT3 overexpression diminished AT-II-mediated apoptotic effects and inhibiting effects on expressions of STAT3 target genes in A375 cells. Interpretation Our results suggest that AT-II inhibits STAT3 signalling and tumour cell growth in melanoma in vivo and in vitro.