Jin-Fu-An decoction manipulation of macrophage polarization via β-catenin (CTNNB1) synergizes with cisplatin in lung cancer

Abstract

Previous studies have demonstrated that tumor-associated macrophages (TAMs) exhibiting an M2 phenotype contribute significantly to the pathogenesis of various cancer types, including lung cancer. Therapeutic approaches targeting TAMs have the potential to complement and synergize with conventional chemotherapy and immunotherapy. Through database analysis, it has become evident that the expression of CTNNB1 (β-catenin) is predominantly localized in macrophages, and its presence is associated with unfavorable outcomes in the absence of CD8+ cells. Jin-Fu-An decoction (JFAD) has been utilized as an adjunct to augment current clinical interventions. By conducting a network pharmacological analysis, we discovered that CTNNB1 is a significant target of JFAD. Experiments were conducted to examine the impact of JFAD on macrophage polarization both in vitro and in vivo. Furthermore, the study investigated the combined effect of JFAD and cisplatin (CDDP) on mitigating adverse reactions and prolonging survival in subcutaneously transplanted tumor models and orthotopic lung cancer models. The percentage of M1 and M2 macrophages in the tumor and spleen were measured using flow cytometry. Additionally, the levels of β-catenin, M1, and M2 macrophage markers were measured by Western blotting and qPCR, while CD8 and iNOS protein expression was analyzed via immunohistochemistry. Our research findings indicate that JFAD has the ability to modulate the transformation of M2 macrophages into M1 macrophages, augment the anticancer efficacy of CDDP, and diminish the expression of cell-related markers in M2 cells. This regulatory effect may potentially be associated with the downregulation of β-catenin expression.