联合治疗通过抑制肝细胞癌中的DNA-PK活性来降低存活激酶AKT和增强细胞凋亡效应半胱天冬酶-8  

Combination Therapy reduced Survival Kinase AKT and enhanced Apoptosis Effector Caspase-8 by suppressing DNA-PK Activity in Hepatocellular Carcinoma

作　　者：陈瑾 字光慧 赵思博 彭保卫 Chen Jin;Zi Guanghui;Zhao Sibo;Peng Baowei(Dali University,Dali 671000;Dali City Jinqiu Moxian Academy Middle School,Dali 671000,China)

机构地区：[1]大理大学,云南大理671000 [2]大理市金秋墨弦书院中学,云南大理671000

出　　处：《广东化工》2023年第17期60-64,91,共6页Guangdong Chemical Industry

摘　　要：AKT的PI3K依赖性磷酸化和活化广泛分布,这反过来又导致增殖和细胞存活率增强,AKT在应对DNA损伤时被激活。本研究旨在探讨DNA损伤与半胱天冬酶-8之间的相互作用以及DNA-PK对肝癌自噬和细胞凋亡的影响。我们的结果表明,PIK75和cisplatin(顺铂)联合治疗增加了HepG2细胞的细胞凋亡,减少了AKT的磷酸化,PI3K抑制剂PIK75通过抑制DNA-PK活性增加了HepG2细胞的凋亡。此外,DNA-PK的消耗抑制AKT的积累,减少了细胞活力。DNA损伤诱导的AKT-pSer473以PI3K依赖性方式促进细胞凋亡和自噬。PI3K-dependent phosphorylation and activation of Akt is wide spread,which in turn leads to enhanced proliferation and cell survival,AKT is activated in response to DNA damage.This study aims to explore the interaction between DNA damage and caspase-8 and the effect of DNA-PK on autophagy and apoptosis in liver cancer.Our results suggest that combination therapy with PIK75 and cisplatin increases apoptosis in HepG2 cells and reduces phosphorylation of AKT,and the PI3K inhibitor PIK75 increases apoptosis in HepG2 cells by inhibiting DNA-PK activity.In addition,the consumption of DNA-PK inhibits the accumulation of AKT and reduces cell viability.DNA damage-induced AKT-pSer473 promotes apoptosis and autophagy in a PI3K-dependent manner.

关 键 词：DNA-PK 细胞凋亡 联合治疗 AKT 肝细胞癌 

分 类 号：R96[医药卫生—药理学]