Cancer Management and Research (Feb 2021)
Sevoflurane Limits Glioma Progression by Regulating Cell Proliferation, Apoptosis, Migration, and Invasion via miR-218-5p/DEK/β-Catenin Axis in Glioma
Abstract
Yingying Qi, Lina Guo, Yanchao Liu, Tonghang Zhao, Xianwen Liu, Yang Zhang Department of Anesthesiology, Liaocheng People’s Hospital, Liaocheng, Shandong, People’s Republic of ChinaCorrespondence: Yang ZhangDepartment of Anesthesiology, Liaocheng People’s Hospital, No. 67, Dongchang West Road, Liaocheng, 252000, Shandong, People’s Republic of ChinaTel +86-0635-8276414Email [email protected]: Sevoflurane (SEV) is a frequently used volatile anesthetic in cancer surgery. Sevoflurane treatment has been shown to suppress the migration and invasion of several human cancer cells. However, the effect of sevoflurane on glioma remains largely unclear.Methods: Glioma cell lines (U251 and U343) were treated by various concentrations of sevoflurane. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry assay, and transwell assay were performed to detect the cell viability, apoptosis, migration and invasion. Western blot assay was employed to detect the protein levels of β-catenin, c-Myc, CyclinD1, β-catenin, N-cadherin, vimentin, and DEK. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the expression level of miR-218-5p. The target interaction between miR-218-5p and DEK was predicted through bioinformatics analysis and verified by dual-luciferase reporter assay system.Results: We found that sevoflurane aberrantly inhibited the abilities on viability, migration, invasion, EMT and β-catenin signaling and promoted cell apoptosis in U251 and U343 cells in a dose-dependent manner. MiR-218-5p strikingly suppressed the abilities of proliferation, migration, invasion rather than apoptosis and activation of β-catenin signaling. Sevoflurane could facilitate the miR-218-5p expression, and its suppressing effects on glioma cells were reversed by pre-treatment with miR-218-5p inhibitors or pcDNA3.1/DEK in vitro and in vivo. Silencing of miR-218-5p reverted sh-DEK and sevoflurane-induced repression on proliferation, migration, invasion, and β-catenin signaling, and promotion on apoptosis in the glioma cells.Conclusion: Our data showed that sevoflurane inhibited the proliferation, migration, invasion, and enhanced the apoptosis in glioma cells through regulating miR-218-5p/DEK/β-catenin axis.Keywords: glioma, sevoflurane, miR-218-5p, DEK, β-catenin signaling pathway
