RESUMO
We investigated the efficacy of Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, in melanoma. We found that ALS exerts anti-proliferative, pro-apoptotic, and pro-autophagic effects on A375 and skmel-5 melanoma cells by inhibiting p38 MAPK signaling. SB202190, a p38 MAPK-selective inhibitor, enhanced ALS-induced apoptosis and autophagy in both cell lines. ALS induced cell cycle arrest in melanoma cells through activation of the p53/p21/cyclin B1 pathway. Knockdown of p38 MAPK enhanced ALS-induced apoptosis and reduced ALS-induced autophagy. Inhibition of autophagy sensitized melanoma cells to ALS-induced apoptosis. These data indicate ALS is a potential therapeutic agent for melanoma.
RESUMO
OBJECTIVE: To determine the effect of doxorubicin (DOX) on abcb4 gene expression and the role of abcb4 gene in multidrug-resistance. METHODS: Zebrafish embryos were treated with 2 mL/L DMSO, 10 µmol/L DOX and 2 mL/L DMSO+10 µmol/L DOX, respectively. The zebrafish embryos treated with Eggwater served as controls. Exposures started at 4 to 16 cell stage of the embryos and terminated 120 hours post fertilization (hpf). The expression of abcb4 gene in zebrafish embryos was examined on 48, 72, 96, and 120 hpf with whole-mount in situ hybridization (WISH) and quantitative real-time PCR (qPCR). RESULTS: Compared with the controls, DOX-exposed embryos had higher level of abcb4 gene expression (P < 0.05), but not for abcb5 gene. WISH showed that abcb4 gene was expressed in the guts of zebrafish embryos. However, those exposed to DOX also showed strong WISH signals in the brain and heart. CONCLUSION: Doxorubicin increases the expression of abcb4 gene in zebrafish embryos. abcb4 gene may play an imoortant role in multidrug-resistance.
