Sevoflurane promotes migration,invasion,and colony-forming ability of human glioblastoma cells possibly via increasing the expression of cell surface protein 44  

作　　者：Ren-chun Lai Wei-ran Shan Di Zhou Xiao-qing Zeng Kendrick Zuo Dong-feng Pan Wei-an Zeng Zhi-yi Zuo 

机构地区：[1]Department of Anesthesiology,University of Virginia,Charlottesville,VA 22901,USA [2]State Key Laboratory of Oncology in South China,Collaborative Innovation Center or Cancer Medicine,Department of Anesthesiology,Sun Yat-Sen University Cancer Center,Guangzhou 510060,China [3]Department of Anesthesiology,Zhongshan Hospital,Fudan University,Shanghai 200032,China [4]Department of Radiology and Biomedical Imaging,University of Virginia,Charlottesville,VA 22908,USA

出　　处：《Acta Pharmacologica Sinica》2019年第11期1424-1435,共12页中国药理学报（英文版）

摘　　要：Surgical resection of primary solid tumor under anesthesia remains a common practice.It has been concerned whether general anesthetics,especially volatile anesthetics,may promote the growth,migration,and invasion of cancer cells.In this study,we examined the effects of sevo?urane on human glioblastoma cells and determined the role of cluster of differentiation(CD)44,a cell surface protein involved in cell growth,migration,and invasion,in sevo?urane’s effects.We showed that exposure to 1%–4%sevo?urane did not change the cell proliferation,but concentration-dependently increased the invasion of human glioblastoma U251 cells.Furthermore,4%sevo?urane signi?cantly increased the migration and colony-forming ability of U251 cells.Similar results were observed in human glioblastoma A172 cells.Exposure to sevo?urane concentration-dependently increased the activity of calpains,a group of cysteine proteinases,and CD44 protein in U251 and A172 cells.Knockdown of CD44 with siRNA abolished sevo?urane-induced increases in calpain activity,migration,invasion,and colony-forming ability of U251 cells.Inhalation of 4%sevo?urane signi?cantly increased the tumor volume and invasion/migration distance of U87 cells from the tumor mass in the nude mice bearing human glioblastoma U87 xenograft in the brain.The aggravation by sevo?urane was attenuated by CD44 silencing.In conclusion,sevo?urane increases the migration,invasion,and colony-forming ability of human glioblastoma cells in vitro,and their tumor volume and invasion/migration in vivo.Sevo?urane enhances these cancer cell biology features via increasing the expression of CD44.

关 键 词：SEVOFLURANE anesthetics CALPAINS CD44 HUMAN glioblastoma INVASION MIGRATION COLONY forming 

分 类 号：R73[医药卫生—肿瘤]