Combined amlexanox and anti-MCP-1 therapy suppresses tumor progression in a murine Lewis lung carcinoma model.

This study aims to assess the effects of combined amlexanox and an antimonocyte chemoattractant protein-1 (MCP-1) mAb therapy in a murine Lewis lung carcinoma (LLC) model. A subcutaneous LLC model was established in mice, which were allocated to either a control group or an intervention group receiving combined amlexanox and anti-MCP-1 mAb. Tumor size was monitored regularly. Immunofluorescence staining was performed to detect MCP-1 and Ki67 expression. Western blot analysis was conducted to assess the expression of TANK-binding kinase 1 (TBK1), macrophage polarization markers (iNOS and arginase-1), and apoptosis-related proteins (MCL-1, Bcl-xL, and Bcl-2). Flow cytometry was employed to quantify macrophage phenotype distributions. TBK1 expression was significantly elevated in LLC tumor tissues. MCP-1 was found to colocalize with the M2 macrophage marker CD206. The combination therapy resulted in a significant reduction in Ki67 expression. arginase-1 expression decreased significantly, while iNOS expression indicated an upward trend, though the change was not statistically significant. Levels of the antiapoptotic proteins MCL-1 and Bcl-xL were significantly downregulated (P < 0.05), whereas Bcl-2 levels did not differ significantly from those in the control group (P > 0.05). Flow cytometric analysis indicated a significant decrease in M2 macrophages (F4/80+CD206+) in the intervention group, with no substantial change observed in the proportion of M1 macrophages (F4/80+CD86+). Combined administration of amlexanox and anti-MCP-1 mAb inhibited tumor cell proliferation, promoted apoptosis, and reduced infiltration of tumor-associated M2 macrophages, thereby contributing to suppression of tumor progression in the LLC murine model.