Stigmasterol Inhibits Glioma Metastasis and Angiogenesis by Regulating Macrophage Polarization

Stigmasterol exhibits broad-spectrum anticancer effects, but whether it exerts anti-glioma effects through modulation of macrophage polarization remains unclear. Mouse bone marrow-derived macrophages (BMDMs) were isolated and induced to polarize into M1 and M2 macrophages to obtain conditioned media (CM). GL261 cells were treated with CM and stigmasterol to evaluate their effects on cell function. Murine subcutaneous and metastatic tumor models were established. Cell viability, angiogenesis, migration, and invasion capacities were assessed using Cell Counting Kit-8, tube formation, wound healing, and Transwell assays, respectively. Reverse transcription-quantitative polymerase chain reaction, immunoblotting, immunofluorescence, and immunohistochemical staining were employed to measure mRNA and protein expression levels. Macrophage polarization was analyzed by flow cytometry. The results showed that stigmasterol inhibited glioma growth both in vitro and in vivo and reduced angiogenesis in HUVECs. Moreover, stigmasterol blocked the M2 macrophage-mediated promotion of glioma growth and angiogenesis in HUVECs. The expression of metastasis-related proteins and angiogenic factors in glioma cells induced by M2 macrophages was inhibited by stigmasterol treatment. Furthermore, stigmasterol attenuated macrophage polarization and restrained glioma formation and metastasis in vivo. This study shows that stigmasterol can suppress M2 macrophage polarization to inhibit the progression of gliomas, providing a potential therapeutic compound for glioma treatment.