MTHFD2對腦膠質母細胞瘤細胞生長和轉移的作用和機制研究

【中圖分類號】R739.41【文獻標志碼】A【文章編號】1672-7770（2025）02-0166-08

Abstract： Objective To explore the effects methylenetetrahydrolate dehydrogenase 2 （MTHFD2） on the growth and metastasis glioblastoma（GBM） cells and its mechanism. Methods The expression level MTHFD2 in GBM tissues and normal tissues was analyzed by interactive gene expression prile analysis database（GEPIA）. U87 MG cells were divided into control group， si-NC group and si-MTHFD2 group. The changes glycolysis and oxidative stress， as well as cell proliferation， apoptosis， migration and invasion were detected in each group. Xenotransplantation model nude mice was established and divided into sh-NC group and sh-MTHFD2 group. Tumor volume was measured and tumor growth curve was drawn. The expression levels MTHFD2 gene were detected by RT-qPCR， and the expression levels glycolysis key enzymes and epithelialmesenchymal transition marker proteins were detected by Western blot. Results GEPIA database analysis showed that MTHFD2 was highly expressed in GBM tissues （ ）. Compared with normal NHA cells， the relative expression levels MTHFD2 mRNA and protein in U87 MG cells were increased （ ）. Silence MTHFD2 inhibited the relative glucose intake and lactate production U87 MG cells， inhibited clone formation， cell proliferation activity， cell migration and invasion， and promoted the level oxidative stress and cell apoptosis.In the tumor formation experiment nude mice， silence MTHFD2 inhibited tumor growth. Conclusions MTHFD2 is a promoter malignant progression GBM. The silencing MTHFD2 expression can effctively inhibit cellular glycolysis stress， suppress cell proliferation， migration， invasion， and tumorigenesis in vivo， while also enhancing oxidative stress and apoptosis.

Key words： glioblastoma； methylenetetrahydrolate dehydrogenase 2； glycolysis； oxidativestress； proliferation and apoptosis； migration and invasion

膠質母細胞瘤（glioblastoma，GBM）起源于星形膠質細胞，是最具侵襲性和最常見的惡性原發性腦腫瘤，根據世界衛生組織分類，屬于高級別惡性膠質瘤（IV級）[1]。GBM這種高度侵襲性的癌癥臨床預后較差，總體5年的相對存活率在所有癌癥類型中非常低[2]。目前主要的治療方式包括手術切除、放療和化療治療，而免疫療法和靶向療法也是目前針對 GBM 的熱門療法，但臨床治療效果仍不理想[3]因此，研究GBM的生物學特性和病理進展機制，尋找抑制GBM生長和轉移的新機制和新視角，對于GBM的治療具有重要意義。

亞甲基四氫葉酸脫氫酶2（methylenetetrahydrolatedehydrogenase2，MTHFD2）是參與線粒體葉酸一碳代謝的重要酶類，在NADP（H）輔因子的再生和維持中發揮重要作用，以增強氧化還原防御并維持細胞快速生長的生物合成反應[。MTHFD2已被發現在各種癌組織和細胞中表達上調，相反，腫瘤中MTHFD2的缺失可能會抑制癌癥的惡性進展，并引發癌細胞死亡，因此推測MTHFD2過度表達會導致癌癥進展，且與侵襲性臨床病理參數、轉移和較短的生存期有關[]。MTHFD2在GBM中的作用和機制并未得到全面解析，本研究旨在從細胞水平解析MTHFD2在GBM細胞中的作用，以期為MTHFD2作為GBM臨床靶標藥物的研發提供可能的選擇。

1資料與方法

1.1實驗試劑葡萄糖含量檢測試劑盒、乳酸含量檢測試劑盒、丙二醛（malondialdehyde，MDA）含量檢測試劑盒、超氧化物歧化酶（superoxidedismutase，SOD）活性檢測試劑盒、谷胱甘肽過氧化物酶（ glutathione peroxidase， ）活性檢測試劑盒和Matrigel（基底膠）均購自北京索萊寶科技有限公司。CCK-8試劑盒和TUNEL細胞凋亡檢測試劑盒（紅色熒光）購自碧云天生物技術研究所。……