Anti-metastatic effects of AGS-30 on breast cancer through the inhibition of M2-like macrophage polarization - 29/02/24
Abstract |
AGS-30, a new andrographolide derivative, showed significant anticancer and anti-angiogenic characteristics. However, its role in controlling macrophage polarization and tumor immune response is unknown. Thus, the main goals of this study are to investigate how AGS-30 regulates macrophage polarization and how it suppresses breast cancer metastasis. AGS-30 inhibited IL-4 and IL-13-induced RAW 264.7 and THP-1 macrophages into M2-like phenotype. However, AGS-30 did not affect the LPS and IFN-γ-induced polarization of M1-like macrophages. AGS-30 reduced the mRNA expressions of CD206, Arg-1, Fizz-1, Ym-1, VEGF, IL-10, MMP2, and MMP9 in M2-like macrophages in a concentration-dependent manner. In contrast, andrographolide treatment at 5 μM did not affect M1-like and M2-like macrophage polarization. The conditioned medium from M2-like macrophages increased 4T1 breast cancer cell migration and invasion, whereas AGS-30 inhibited these effects. In the 4T1 breast tumor xenograft mice, the tumor volume and weight were reduced without affecting body weight after receiving AGS-30. AGS-30 treatment also reduced lung and liver metastasis, with reduced STAT6, CD31, VEGF, and Ki67 protein expressions. Moreover, the tumors had considerably fewer M2-like macrophages and Arg-1 expression, but the proportion of M1-like macrophages and iNOS expression increased after AGS-30 treatment. Same results were found in the tail vein metastasis model. In conclusion, this study shows that AGS-30 inhibits breast cancer growth and metastasis, probably through inhibiting M2-like macrophage polarization. Our findings suggest that AGS-30 may be a potential immunotherapeutic alternative for metastatic breast cancer.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | AGS-30 shows stronger effects than Andro in suppressing M2-like macrophage polarization |
• | AGS-30 suppresses M2 macrophages-induced angiogenesis and cancer cell mobility in vitro |
• | AGS-30 suppresses breast cancer metastasis by regulating macrophage polarization and activating T cells |
Abbreviations : Andro, Arg-1, CD31, ELISA, H&E, HUVECs, IFN-γ, IL, iNOS, LDH, LPS, MFI, MMP, PMA, qPCR, STAT6, TNF-α, VEGF
Keywords : Andrographolide derivative, Breast cancer, Macrophage polarization, Cancer metastasis.
Plan
Vol 172
Article 116269- mars 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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