Shang Yuan-Yuan, Yao Ming, Zhou Zhi-Wei, Hu Rong-Ying, Yu Ying-Yao, Liu Yu-Xi, Dang Jie, Zhou Shu-Feng
Department of Dermatology, General Hospital of NingXia Medical University, Yinchuan, P.R.China.
Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.
Oncotarget. 2017 Nov 6;8(63):107076-107088. doi: 10.18632/oncotarget.22328. eCollection 2017 Dec 5.
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.
我们研究了选择性极光激酶A（AURKA）抑制剂阿利西替尼（ALS）在黑色素瘤中的疗效。我们发现，ALS通过抑制p38丝裂原活化蛋白激酶（MAPK）信号传导，对A375和skmel-5黑色素瘤细胞发挥抗增殖、促凋亡和促自噬作用。p38 MAPK选择性抑制剂SB202190增强了ALS诱导的这两种细胞系的凋亡和自噬。ALS通过激活p53/p21/细胞周期蛋白B1途径诱导黑色素瘤细胞的细胞周期停滞。敲低p38 MAPK增强了ALS诱导的凋亡并减少了ALS诱导的自噬。抑制自噬使黑色素瘤细胞对ALS诱导的凋亡敏感。这些数据表明，ALS是黑色素瘤的一种潜在治疗药物。
