成纤维细胞生长因子（FGF）参与神经胶质瘤（最常见的脑肿瘤类型）和乳腺肿瘤的进展。在本研究中，我们旨在评估抑制剂 PP2 对神经胶质瘤和乳腺肿瘤细胞增殖和迁移的影响，并表征这些过程中涉及的分子机制。通过增殖、迁移和侵袭测定以及细胞凋亡分析来检查 PP2 对 C6 胶质瘤和 MDA-MB-231 细胞致瘤潜力的抑制作用。通过免疫印迹、免疫沉淀、磷蛋白测定、细胞热位移测定 (CETSA) 和分子对接模型研究了 PP2 抗神经胶质瘤活性背后的分子机制。 PP2 通过 FGF2 抑制 C6 神经胶质瘤和 MDA-MB-231 细胞的增殖和迁移。此外，PP2直接阻断FGF受体1（FGFR1）和Src的酶活性，随后影响核因子-κB和激活蛋白-1信号通路。 CETSA分析和对接模型表明FGFR2的TK1结构域(Val 492和Glu 486)可能是PP2的结合位点。因此，总的来说，我们的研究结果表明，PP2 通过靶向 FGFR1 和 Src 介导抗肿瘤作用，并可能作为治疗性抑制剂用于治疗神经胶质瘤。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Fibroblast growth factor (FGF) is involved in the progression of glioma, a most common type of brain tumor, and breast tumors. In this study, we aim to evaluate the effects of the inhibitor PP2 on cell proliferation and migration in glioma and breast tumor cells, and to characterize the molecular mechanisms involved in these processes. The inhibitory effect of PP2 on the tumorigenic potential of C6 glioma and MDA-MB-231 cells was examined by proliferation, migration, and invasion assays, and apoptotic analysis. The molecular mechanism behind the anti-glioma activity of PP2 was investigated by immunoblotting, immunoprecipitation, phosphoprotein assay, cellular thermal shift assay (CETSA), and molecular docking modeling. PP2 suppressed the proliferation and migration of C6 glioma and MDA-MB-231 cells via FGF2. Moreover, PP2 directly blocked the enzyme activity of FGF receptor 1 (FGFR1) and Src, subsequently affecting the nuclear factor-κB and activator protein-1 signaling pathways. CETSA analysis and the docking model indicated that the TK1 domains (Val 492 ad Glu 486) of FGFR2 could be binding sites of PP2. Collectively, therefore, our findings suggest that PP2 mediates antitumor effects by targeting both FGFR1 and Src and may have applications as a therapeutic inhibitor for the treatment of glioma.Copyright © 2024 Elsevier B.V. All rights reserved.