阻断VEGFR2通过增强线粒体生物生成来抑制质母细胞细胞的增殖

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Min Guo¹, Junhao Zhang^2,3, Jiang Han⁴

¹Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. guomin04@126.com.

Journal of translational medicine

|May 3, 2024

概括

向质母细胞瘤中的血管内皮生长因子受体2 (VEGFR2) 会阻止瘤的生长,并诱导亡. 这发生在通过通过AKT-PGC1α-TFAM通路增强的线粒体生物发生过程中,这表明VEGFR2阻断是潜在的质母细胞瘤治疗.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

质母细胞瘤是一种具有侵略性的脑瘤,其特点是广泛的血管生成和患者的不良结果.
针对血管内皮生长因子受体2 (VEGFR2) 的抗血管性疗法正在探索用于质母细胞瘤治疗.
对VEGFR2阻断对质母细胞瘤细胞的直接影响在很大程度上仍然未被描述.

研究的目的:

研究VEGFR2抑制对质母细胞瘤细胞增殖和亡的影响.
阐明基础分子机制,特别是线粒体生物发生的作用,在VEGFR2-介导的抗质母细胞瘤效应.

主要方法:

从癌症基因组图谱 (TCGA) 获取了用于质瘤患者的VEGFR2表达数据.
在VEGFR2干预中使用了选择性VEGFR2抑制剂 (Ki8751) 和短毛RNA (shRNA).
通过免疫光成像,质谱学和西部斑分析,评估了质母细胞细胞中的线粒体生物发生.

主要成果:

升高的VEGFR2表达与较高的 Glioma 恶性病 (III 和 IV 级) 相关联.
抑制VEGFR2显著降低了质母细胞瘤细胞增殖和诱导的亡.
VEGFR2阻断促进了线粒体生物发生,其证据是线粒体质量增加,氧化酸化 (OXPHOS) 和反应性氧物种 (ROS) 生产.
抑制VEGFR2降低了AKT和PGC1α酸化的调节,导致PGC1α核转位,增加TFAM表达,并随后增强了线粒体生物发生.

结论:

阻断VEGFR2有效地通过AKT-PGC1α-TFAM介导的线粒体生物发生路径抑制质母细胞瘤的进展.
干预VEGFR2显示出作为治疗质母细胞瘤治疗的附加治疗策略的潜力.

关键词:

质母细胞瘤 (glioblastoma) 是一个线粒体中的线粒体.线粒体转录因子A 线粒体转录因子A 过氧体增殖器激活的受体玛联合激活剂1-α/PGC1αα.有反应性氧物种的反应性氧物种.血管内皮生长因子受体2

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