ArticleBiological procedures online2025
(-)-Guaiol Downregulates M2 Tumor-Associated Macrophage Polarization Through PPAR-γ Signaling to Suppress Lung Cancer.
Article in Biological procedures online, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundM2 macrophages play a pivotal role in promoting the growth and metastasis of lung cancer cells. Inhibiting M2 macrophage polarization represents an effective immunotherapeutic approach against tumors. Although (-)-Guaiol has been shown to exert potent inhibitory effects on M2 macrophage polarization, its underlying molecular mechanism remains unclear.
objectiveThis study aimed to elucidate the effects of (-)-Guaiol on M2 macrophage polarization and to explore the potential molecular mechanisms involved.
methodsBone marrow-derived macrophages (BMDMs) from mice were polarized toward the M2 phenotype using IL-4 and M-CSF. Both ex vivo and in vivo experiments were performed to determine whether (-)-Guaiol suppresses M2 macrophage polarization through the PPAR-γ-related signaling pathway. PPAR-γ agonists and inhibitors were applied to confirm the involvement of PPAR-γ in the effects of (-)-Guaiol. A co-culture system of M2 macrophages and Lewis lung carcinoma (LLC) cells was established. Wound healing, Transwell invasion, and plate cloning experiments were performed to determine the effects of (-)-Guaiol on the metastasis and development of lung cancer cells.
results(-)-Guaiol markedly downregulated the expression of CD206, a characteristic surface marker of M2-polarized macrophages. It also significantly inhibited the proliferation, invasion, and metastatic potential of LLC cells co-cultured with M2 macrophages. Animal experiments revealed that (-)-Guaiol treatment significantly decreased the tumor volume and weight, as well as CD206 expression. Moreover, integrated in vitro and in vivo analyses revealed that (-)-Guaiol inhibited M2 macrophage polarization primarily by suppressing the PPAR-γ signaling pathway.
conclusionThese findings demonstrate that (-)-Guaiol inhibits M2 macrophage differentiation via targeted suppression of the PPAR-γ-related signaling pathway, thereby reducing the proliferation, migration, and invasion of lung cancer cells.
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