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Raf/MEK/ERK Signaling Pathway Is Involved in the Inhibition of Glioma Cell Proliferation and Invasion in the Ketogenic Microenvironment

作     者:Wen-tao FAN Xiao-fei LIU LIU Ri-chu LIANG Wen-tao FAN;Xiao-fei LIU;Ri-chu LIANG

作者机构:Department of NeurosurgeryThe Second Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421000China 

出 版 物:《Current Medical Science》 (当代医学科学(英文))

年 卷 期:2023年第43卷第4期

页      面:759-767页

核心收录:

学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基  金:supported by the Clinical Innovation Guidance Plan of the Department of Science and Technology of Hunan Province(No.2018SK51502) a Postgraduate Scientific Research Innovation Project of Hunan Province(No.CX20210977) Key Guiding Subjects of the Hunan Provincial Health Commission(No.20201912) the Natural Science Foundation of Hunan Province(Nos.2020JJ8029,2018JJ3461) 

主  题:glioma ketogenic microenvironment Raf/MEK/ERK 

摘      要:Objective:A high-fat,low-carbohydrate ketogenic diet has been used to treat malignant glioma,in which the Raf/MEK/ERK signaling pathway is ***,whether the Raf/MEK/ERK signaling pathway is involved in the therapeutic effect of ketone bodies remains *** this study,we investigated the effects of a major ketone body,3-hydroxybutyric acid(3-HBA),on the proliferation and metastasis of malignant glioblastoma cells and the underlying ***:Two human malignant glioblastoma cell lines(U87 and U251)were treated with different concentrations of 3-HBA with or without the Raf inhibitor PAF C-16 for 24 *** proliferation,cell cycle,cell invasion,and phospholipase D1(PLD1)activity were *** and gene expression levels of Raf/MEK/ERK signaling pathway members were ***:3-HBA significantly decreased cell proliferation,invasion,and intracellular PLD1 activity in both U87 and U251 glioblastoma cell lines.3-HBA treatment significantly increased the proportion of cells in the G1 phase and decreased the proportion of cells in S phase in U87 *** the U251 line,the proportion of treated cells in S phase was increased and proportion of cells in G2 was decreased.3-HBA treatment also significantly decreased the protein expression levels of Raf,MEK,p-MEK,ERK,p-ERK,and PLD1 while increasing p53 expression;an effect that was similar to treatment with the Raf ***-treatment of 3-HBA with the Raf inhibitor further enhanced the effects of the 3-HBA in both cell ***:We confirmed that a ketogenic microenvironment can inhibit glioma cell proliferation and invasion by downregulating the expression of PLD1 through the Raf/MEK/ERK signaling pathway.

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