多形性胶质母细胞瘤（GBM）是最常见的原发性颅内肿瘤，具有侵袭性高、预后差的特点。德桂林（Deguelin）是来自豆科植物（Leguminosae Mundulea sericea）（非洲植物）树皮的成分，在某些肿瘤中表现出抗增殖作用，然而，德桂林对GBM的抑制作用和机制仍知之甚少。首先，我们发现德桂林通过引起细胞周期停滞在G2/M期并诱导其凋亡来降低GBM细胞的活力。其次，deguelin抑制GBM细胞的迁移。接下来，RNA-seq 分析发现，CCL2（编码一种重要的趋化因子 CCL2）在经九皮胶处理的 GBM 细胞中显着下调。据报道，CCL2通过NFκB信号通路促进GBM细胞的活力、迁移并抑制GBM细胞的凋亡，并调节GBM肿瘤微环境（TME）以促进GBM进展。此外，我们发现CCL2可以通过NFκB信号通路挽救deguelin对GBM细胞的抗抑制作用。最后，我们建立了同基因颅内原位 GBM 模型，发现 deguelin 可以抑制肿瘤生长，促进免疫抑制性 TME，并通过体内抑制 CCL2/NFκB 来抑制 GBM 血管生成。综上所述，这些结果表明德桂林通过抑制 CCL2/NFκB 通路发挥抗 GBM 作用，这可能为 GBM 的治疗提供新策略。版权所有 © 2024。由 Elsevier Ltd 出版。

Glioblastoma multiforme (GBM) is the most common primary intracranial tumor with characteristics of high aggressiveness and poor prognosis. Deguelin, a component from the bark of Leguminosae Mundulea sericea (African plant), displays antiproliferative effects in some tumors, however, the inhibitory effect and mechanism of deguelin on GBM were still poorly understood. At first, we found that deguelin reduced the viability of GBM cells by causing cell cycle arrest in G2/M phase and inducing their apoptosis. Secondly, deguelin inhibited the migration of GBM cells. Next, RNA-seq analysis identified that CCL2 (encode an important chemokine CCL2) was downregulated significantly in deguelin-treated GBM cells. As reported, CCL2 promoted the cell viability, migration of GBM cells, and inhibited apoptosis of GBM cells via NFκB signaling pathway, as well as modulated the GBM tumor microenvironment (TME) to facilitate the GBM progression. Furthermore, we found that CCL2 could rescue the anti-inhibitory effect of deguelin on GBM cells via NFκB signaling pathway. Finally, we established a syngeneic intracranial orthotopic GBM model and found that deguelin regressed the tumor growth, contributed to an immunosuppressive TME and inhibited angiogenesis of GBM by suppressing CCL2/NFκB in vivo. Taken together, these results suggest the anti-GBM effect of deguelin via inhibiting CCL2/NFκB pathway, which may provide a new strategy for the treatment of GBM.Copyright © 2024. Published by Elsevier Ltd.