College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.
Center for Laboratory Medicine, Allergy center, Department of Transfusion medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.
Biomed Pharmacother. 2024 Aug;177:117074. doi: 10.1016/j.biopha.2024.117074. Epub 2024 Jul 6.
Glioma, a common and highly malignant central nervous system tumor, markedly influences patient prognosis via interactions with glioma-associated macrophages. Previous research has revealed the anticancer potential of β-mangostin, a xanthone derivative obtained from the mangosteen fruit. This research investigated the role of β-mangostin on microglia in the glioma microenvironment and evaluated the efficacy of β-mangostin combined with anti-PD-1 antibody (αPD-1) in glioma-bearing mice. The results showed that, β-mangostin attenuated M2 polarization in BV2 cells and promoted M1-related interleukin (IL)-1β and IL-6 secretion, thereby inhibiting glioma invasion. In addition, β-mangostin improved the anti-glioma effects of αPD-1 and increased CD8T cell and M1-type microglia infiltration. Mechanistically, β-mangostin bound to the stimulator of interferon genes (STING) protein, which is crucial for the anti-tumor innate immune response, and promoted STING phosphorylation in microglia, both in vivo and in vitro. These results provide insights into its mode of action and supporting further investigation into β-mangostin as a therapeutic agent.
神经胶质瘤是一种常见且高度恶性的中枢神经系统肿瘤，通过与神经胶质瘤相关的巨噬细胞相互作用显著影响患者的预后。先前的研究揭示了β-倒捻子素的抗癌潜力，β-倒捻子素是从山竹果中提取的一种酮衍生物。本研究探讨了β-倒捻子素对神经胶质瘤微环境中小胶质细胞的作用，并评估了β-倒捻子素与抗 PD-1 抗体（αPD-1）联合治疗荷瘤小鼠的疗效。结果表明，β-倒捻子素可减轻 BV2 细胞的 M2 极化，并促进 M1 相关白细胞介素（IL）-1β和 IL-6 的分泌，从而抑制神经胶质瘤的侵袭。此外，β-倒捻子素增强了 αPD-1 的抗神经胶质瘤作用，并增加了 CD8T 细胞和 M1 型小胶质细胞的浸润。在机制上，β-倒捻子素与干扰素基因刺激蛋白（STING）蛋白结合，STING 蛋白对于抗肿瘤先天免疫反应至关重要，并且在体内和体外均促进小胶质细胞中 STING 的磷酸化。这些结果为其作用模式提供了深入了解，并支持进一步研究β-倒捻子素作为治疗剂的潜力。
