癌症研究
肺癌
活力测定
细胞周期蛋白依赖激酶
克隆形成试验
细胞周期
车站3
细胞凋亡
MTT法
生物
细胞周期蛋白D1
污渍
流式细胞术
癌症
分子生物学
医学
病理
生物化学
基因
遗传学
作者
Feng Zhou,Fanyun Zhu,Tianru Zhu,Zhucheng Zhao,Luyao Li,Shichong Lin,Haiyang Zhao,Lehe Yang,Chengguang Zhao,Liangxing Wang,Jifa Li,Xiaoying Huang
标识
DOI:10.1016/j.bbrc.2022.03.147
摘要
Lung cancer is a part of the commonest malignancies with the highest mortality rate in cancer-related deaths worldwide. Signal transducer and activator of transcription 3 (STAT3) and cyclin-dependent kinases (CDKs) are promising prognostic marker and therapeutic target in cancers. Our previous study has demonstrated the closely relationship between CDK9 and STAT3 in lung cancer. The inhibition of cell viability and migration in vitro by AT7519 were evaluated using methyl thiazolyl tetrazolium (MTT) assay, clonogenic assay and scratch wound model. The cell cycle analysis was evaluated using flow cytometry analysis and western blotting analysis. The apoptotic-induced efficiency was assessed by flow cytometry analysis, hoechst 33342 staining, caspase-3 activity analysis and western blotting analysis. The roles of STAT3 in AT7519 treatment for lung cancer were assessed by docking model and western blotting analysis. The patient-derived xenograft (PDX) models were used to investigate the effect of AT7519 in vivo. In this study, we found that AT7519, a CDK inhibitor, reduced the viability of lung cancer cells in vitro and strongly suppressed tumor growth in PDX model. AT7519 blocked cell cycle progression and induced apoptosis by inhibiting IL-6/STAT3 pathway. Taken together, AT519 exhibits great anti-tumor effects in lung cancer, and the mechanism was related closely to IL-6/STAT3 signaling pathway, which suggests the important roles of STAT3 in CDKs inhibitors. AT7519 might be a novel potential therapeutic agent based on this rationale.
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