5-HMF抑制A375细胞增殖的信号转导通路

The signaling pathway of 5-HMF-induced A375 cell growth inhibition

通过Caspase活性检测和Western blotting法对ROS介导的A375细胞凋亡和G0/G1细胞周期阻滞中相关蛋白进行分析。结果表明:5-HMF通过清除细胞内ROS激活了DNA损伤介导的P53磷酸化、AKT通路和MAPKs通路,这些通路共同作用于相应的下游底物,激活外源性的死亡受体通路和内源性的线粒体通路导致细胞的凋亡,其中,5-HMF通过上调线粒体中的促凋亡因子、下调抑凋亡因子并活化Bid而激活內源性途径;此外,P53、AKT等也可以抑制或增强G0/G1期主要调控因子的表达,导致G0/G1期阻滞,证明了5-HMF可抑制A375细胞增殖的信号转导通路。

The proteins that regulate A375 cell apoptosis and G0/G1 cell cycle arrest were investigated by Caspase activity assay and Western blot analysis.The results show that 5-HMF induces DNA damage-mediated the expression of P53 and phosphorylates,activates AKT and MAPKs pathways which can activate the downstream death receptor-mediated extrinsic and mitochondria-mediated intrinsic pathways.Among them,5-HMF triggeres intrinsic pathway via up-regulation pro-apoptotic factors,downregulation anti-apoptotic factor reduction and activation of Bid.In addition,P53 and AKT also can inhibit or enhance the regulating factor expression of the G0/G1 phase,leading to G0/G1 cell cycle arrest.In summary,the signaling pathway of 5-HMF-induced A375 cell growth inhibition was demonstrated.