宁夏医科大学学报2024,Vol.46Issue(6) :541-546.DOI:10.16050/j.cnki.issn1674-6309.2024.06.001

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

曹瑜 张亚军 杨丽娜 马泽梅 曹相玫 张宁妹
宁夏医科大学学报2024,Vol.46Issue(6) :541-546.DOI:10.16050/j.cnki.issn1674-6309.2024.06.001

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

曹瑜 1张亚军 2杨丽娜 1马泽梅 1曹相玫 1张宁妹3
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作者信息

  • 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
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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(doxycy-cline)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.

Abstract

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

Key words

vitamin C/glioma/isocitrate dehydrogenase/apoptosis/invasion

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基金项目

宁夏回族自治区自然科学基金(2022AAC03549)

出版年

2024
宁夏医科大学学报
宁夏医科大学

宁夏医科大学学报

CSTPCD
影响因子:0.84
ISSN:1674-6309
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