喹唑啉类PAK4小分子抑制剂CWS-6抑制胰腺癌细胞增殖、迁移和侵袭  

Inhibitory effect of quinazoline PAK4 small molecule inhibitor CWS-6 on proliferation,migration and invasion of pancreatic cancer cells

作　　者：袁莹[1] 李晓东[1] YUAN Ying;LI Xiaodong(Department of Cell Biology,Key Laboratory of Cell Biology,Ministry of Public Health,and Key Laboratory of Medical Cell Biology,Ministry of Education,China Medical University,Liaoning Shenyang 110122,China)

机构地区：[1]中国医科大学生命科学学院分子细胞生物学教研室,教育部医学细胞生物学重点实验室,辽宁沈阳110122

出　　处：《现代肿瘤医学》2021年第18期3160-3166,共7页Journal of Modern Oncology

基　　金：辽宁省教育厅科学研究经费(编号:JC2019030)。

摘　　要：目的:探究喹唑啉类PAK4小分子抑制剂CWS-6对胰腺癌细胞增殖、迁移、侵袭等方面的作用。方法:CCK8检测CWS-6对胰腺癌细胞增殖的影响;流式细胞术检测CWS-6对胰腺癌细胞周期分布的影响;细胞划痕实验检测CWS-6对胰腺癌细胞迁移的影响;Transwell实验检测CWS-6对胰腺癌细胞侵袭的影响;激光扫描共聚焦显微(Confocal)实验检测CWS-6对胰腺癌细胞微丝的影响;Western blotting实验检测CWS-6对胰腺癌细胞PAK4激酶的活化及其下游与迁移侵袭相关蛋白表达的影响。结果:CWS-6对胰腺癌细胞的增殖以及周期影响不明显;在5μmol/L时对胰腺癌细胞的迁移及侵袭能力有显著的抑制作用;CWS-6对PAK4激酶的活性以及PAK4下游的细胞骨架相关靶蛋白的表达有抑制作用。结论:CWS-6是通过抑制PAK4激酶的活性来抑制细胞增殖以及通过影响PAK4下游细胞骨架相关蛋白抑制微丝的解聚从而抑制胰腺癌细胞的迁移及侵袭能力。Objective:To investigate the effect of the quinazoline PAK4 small moleculer inhibitor CWS-6 on the proliferation,migration and invasion of pancreatic cancer cells lines.Methods:CCK8 detected the effect of CWS-6 on the proliferation of pancreatic cancer cells at 0 h/24 h/48 h/72 h.The cell cycle progression was observed by Flow cytometry.The effect of CWS-6 on the migration of pancreatic cancer cells was detected by Wound-healing assay.The effect of CWS-6 on the invasion was observed by Transwell assay.Confocal assay observed microfilament of CWS-6.Western blotting assay detected the expression of the activity of PAK4 and also the related proteins with migration and invasion of CWS-6 in pancreatic cancer cells.Results:CWS-6 has no inhibitory effect on the proliferation and cell cycle the of pancreatic cancer cells,but it inhibits the migration and invasion of pancreatic cancer cells at 5μmol/L.It also suppresses the expression of the activity of PAK4 kinase and the it's downstream proteins relating with cytoskeleton.Conclusion:CWS-6 inhibits cell proliferation,migration and invasion of pancreatic cancer cells by suppressing the activity of PAK4 kinase and the downstream proteins of PAK4 which related to cytoskeleton.

关 键 词：PAK4小分子抑制剂 胰腺癌 增殖 迁移 侵袭 

分 类 号：R735.9[医药卫生—肿瘤]