β-elemene inhibits tumor-promoting in small cell lung cancer by affecting M2 macrophages and TGF-β

M2 macrophages have been implicated in promoting tumor growth and metastasis in various cancers, including small cell lung cancer (SCLC). This study investigated the role of M2 macrophages in SCLC progression and explored the therapeutic potential of β-elemene, a natural compound, in modulating M2 macrophage-mediated tumor promotion.

We differentiated THP-1 monocytes into M2 macrophages using PMA (phorbol 12-myristate 13-acetate), IL-4 (interleukin-4), and IL-13 (interleukin-13). M2 macrophages were co-cultured with the SCLC cell line NCI-H209, and CCK-8, Transwell, and flow cytometry assays were performed. TGF-β expression levels were detected by ELISA. M2 macrophages and NCI-H209 co-cultured cells were treated with β-elemene, or M2 macrophages were transfected with TGF-β shRNA lentivirus, and then co-cultured with NCI-H209 cells. Flow cytometry was used to analyze cell apoptosis. Immunofluorescence staining was performed to assess TGF-β expression.

Our findings demonstrate that M2 macrophages significantly enhance the viability, proliferation, and migration of SCLC cells, and this effect is associated with increased TGF-β expression in SCLC cells co-cultured with M2 macrophages. Furthermore, β-elemene treatment significantly reduced the migration and viability of SCLC cells co-cultured with M2 macrophages. Silencing TGF-β expression in M2 macrophages also suppressed SCLC cell proliferation and migration, suggesting that β-elemene may inhibit the pro-tumorigenic effects of M2 macrophages in SCLC by modulating TGF-β signaling. Immunofluorescence staining revealed that β-elemene treatment significantly reduced TGF-β levels in SCLC cells co-cultured with M2 macrophages, supporting the hypothesis that β-elemene exerts its antitumor activity by modulating the TGF-β pathway.

Our results suggest that β-elemene has the potential to suppress SCLC development by modulating M2 macrophages and the TGF-β, offering a new therapeutic avenue and potential drug candidate for SCLC treatment.