维生素C对IDH1突变胶质瘤细胞凋亡和侵袭的影响  

Study on the Effect of Vitamin C on Apoptosis and Invasion in IDH1-Mutant Glioma Cells

作　　者：曹瑜 张亚军 杨丽娜 马泽梅 曹相玫[1] 张宁妹[3] CAO Yu;ZHANG Yajun;YANG Lina;MA Zemei;CAO Xiangmei;ZHANG Ningmei(Department of Pathology,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China;Department of Pathology,Second People's Hospital of Dingxi,Dingxi 743000,China;Department of Pathology,General Hospital of Ningxia Medical University,First Clinical)

机构地区：[1]宁夏医科大学基础医学院病理学研究室,银川750004 [2]定西市第二人民医院病理科,定西743000 [3]宁夏医科大学总医院病理科,宁夏医科大学第一临床医学院,银川750004

出　　处：《宁夏医科大学学报》2024年第6期541-546,共6页Journal of Ningxia Medical University

基　　金：宁夏自然科学基金项目(2022AAC03549)。

摘　　要：目的探讨维生素C(Vitaminc,VC)对异柠檬酸脱氢酶1(IDH1)突变胶质瘤细胞凋亡和侵袭的影响,评价VC在抗胶质瘤治疗中的应用前景。方法以人胶质瘤U87细胞系为基础,用强力霉素(doxycycline)诱导IDH1突变(dox+组),未诱导突变为对照组(dox-),Western blot及免疫荧光检测IDH1突变蛋白表达,CCK-8法检测细胞增殖。进行VC(1 mmol·L^(-1))干预后分为VC干预IDH1突变(dox+VC+)组、无VC干预的IDH1突变(dox+VC-)组、VC干预非IDH1突变(dox-VC+)组、无VC干预的非IDH1突变(dox-VC-)组,用Transwell法检测各组细胞侵袭能力,Western blot检测凋亡、侵袭相关蛋白以及应激相关因子表达,CCK-8法检测细胞增殖情况。结果IDH1突变后dox+组细胞增殖减慢(P<0.05)。VC干预后IDH1突变和非突变胶质瘤细胞的凋亡蛋白Bax、Bad、Cleaved-Caspase-3、Cleaved-PARP表达均上调(P均<0.05),抗凋亡蛋白Bcl-2及侵袭相关蛋白家族成员基质金属蛋白酶(MMP)-7和MMP-9表达均下降(P均<0.01),应急保护蛋白p-HSP27表达上调(P<0.01),细胞侵袭数量降低(P<0.05)。结论VC促进IDH1突变胶质瘤细胞凋亡,抑制其侵袭。Objective To investigate the effects of Vitamin C(VC)on apoptosis and invasion of IDH1-mutant glioma cells,evaluate the potential application of VC in antiglioma therapy.Methods Using the human glioma U87 cell line as a foundation,IDH1 mutation was induced by doxycycline(dox+),while the non-induced mutation served as the control group(dox-).Western blot and immunofluorescence were employed to detect IDH1 mutant protein expression,and cell proliferation was assessed using the CCK-8 method.Four groups were established for VC intervention(1 mmol·L^(-1)):VC intervention IDH1 mutation group(dox+VC+),IDH1 mutation group without VC intervention(dox+VC-),non-IDH1 mutation group with VC intervention(dox-VC+),and non-IDH1 mutation group without VC intervention(dox-VC-).Cell invasion ability was evaluated using the Transwell assay,while Western blot was utilized to detect apoptosis,invasion-related proteins,and stress-related factors expression.Cell proliferation was also assessed using the CCK-8 method.Results Cell proliferation in the dox+group with IDH1 mutation was significantly reduced(P<0.05).After VC intervention,the expression of apoptotic proteins Bax,Bad,Cleaved-caspase-3,Cleaved-PARP in both IDH1-mutant and non-mutant glioma cells was upregulated(P all<0.05),while the anti-apoptotic protein Bcl-2 and invasion-related protein family members MMP-7,MMP-9 expression decreased(P all<0.01).The expression of the stress-protective protein p-HSP27 was upregulated(P<0.01),and the number of invasion cells significantly decreased(P<0.05).Conclusion VC promotes apoptosis and inhibits invasion of IDH1-mutant glioma cells.

关 键 词：维生素C 胶质瘤 异柠檬酸脱氢酶1 凋亡 侵袭 

分 类 号：R739.41[医药卫生—肿瘤]