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血小板衍生生长因子受体α介导的信号传导在胶质母细胞瘤失巢凋亡抗性中的作用:体外研究

Role of PDGFRα-mediated signalling in anoikis resistance in glioblastoma: in vitro study.

作者信息

Raut Sneha, Makwana Meet, Pillai Prakash

机构信息

Division of Neurobiology, Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390002, India.

出版信息

In Vitro Cell Dev Biol Anim. 2025 Jul 21. doi: 10.1007/s11626-025-01075-6.

Abstract

Anoikis resistance, the evasion of programmed cell death when cells detach from the extracellular matrix (ECM), is a critical feature of glioblastoma (GBM) malignancy, contributing to tumor survival, spread, and resistance to therapy. We focused on the role of growth factor receptors, particularly platelet-derived growth factor receptor-α (PDGFRα), and integrin expression patterns in mediating this resistance. We first cultured cells under non-adherent conditions using polyHEMA-treated plates to induce anoikis resistance. We performed assays like cell survival, migration, and sphere formation. To delineate the role of PDGFRα signalling in anoikis resistance, we further employed pharmacological inhibitors of key signalling molecules such as AG1295 (PDGFRα blocker), HS173 (PI3K inhibitor), U0126 (ERK inhibitor), and AG490 (JAK-STAT inhibitor) which led to a decrease in cell survival, proliferation, and migration. These findings highlight the critical role of PDGFRα and associated signalling pathways in mediating anoikis resistance in GBM, offering potential therapeutic targets for intervention.

摘要

失巢凋亡抗性是指细胞从细胞外基质(ECM)脱离时对程序性细胞死亡的逃避,它是胶质母细胞瘤(GBM)恶性肿瘤的一个关键特征,有助于肿瘤的存活、扩散和对治疗的抗性。我们聚焦于生长因子受体,特别是血小板衍生生长因子受体-α(PDGFRα)以及整合素表达模式在介导这种抗性中的作用。我们首先使用经聚甲基丙烯酸羟乙酯(polyHEMA)处理的培养板在非贴壁条件下培养细胞以诱导失巢凋亡抗性。我们进行了细胞存活、迁移和球体形成等检测。为了阐明PDGFRα信号传导在失巢凋亡抗性中的作用,我们进一步使用了关键信号分子的药理学抑制剂,如AG1295(PDGFRα阻断剂)、HS173(PI3K抑制剂)、U0126(ERK抑制剂)和AG490(JAK-STAT抑制剂),这些抑制剂导致细胞存活、增殖和迁移减少。这些发现突出了PDGFRα及相关信号通路在介导GBM失巢凋亡抗性中的关键作用,为干预提供了潜在的治疗靶点。

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