自噬
细胞凋亡
癌症研究
细胞周期
细胞周期蛋白依赖激酶6
细胞周期检查点
细胞周期蛋白D1
细胞
食管癌
活力测定
癌细胞
癌症
化学
医学
内科学
生物化学
作者
Yu Sun,Beibei Sha,Wenjing Huang,Miaomiao Li,Shan Zhao,Yuan Zhang,Jie Yan,Zheng Li,Jingwen Tang,Peiyan Duan,Jianxiang Shi,Pei Li,Tao Hu,Ping Chen
出处
期刊:Apoptosis
[Springer Nature]
日期:2022-06-02
卷期号:27 (7-8): 545-560
被引量:8
标识
DOI:10.1007/s10495-022-01736-x
摘要
Esophageal squamous cell carcinoma (ESCC) is a common digestive cancer with high mortality rate due to late diagnosis and drug resistance. It is important to identify new molecular target and develop new anticancer strategy. ML323 is a novel USP1 inhibitor and exhibits anticancer activity against several cancers. Herein, we investigated whether ML323 has some cytotoxity effect on ESCC cells and explored the underlying mechanisms. Results revealed that ML323 impeded esophageal cancer cell viability and colony formation. Meanwhile, ML323 blocked cells at G0/G1 phase concomitant with the reduced protein level of c-Myc, cyclin D1, CDK4 and CDK6. ML323 treatment also triggered DNA damage and active p53. Then, ML323 induced apoptosis by p53-Noxa. Additionally, it stimulated protective autophagy. Co-treatment with CQ or BafA1, two classical autophagy inhibitors, enhanced the cytotoxity of ML323. These findings suggested that USP1 inhibitor (ML323) could be used as a viable anti-ESCC approach.
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