Inhibitory Effect of Scutellaria barbata D. Don. Extract on Lung Cancer Cell Migration via Regulation of Macrophage Recruitment and Polarization

Scutellaria barbata D. Don has traditionally been used in Korean medicine for its anti-cancer properties. However, most studies on its anti-cancer effects have focused primarily on its direct actions on cancer cells. In this study, we aimed to explore the anti-cancer effects of the ethanolic extract of Scutellaria barbata D. Don (ESBD), with a particular focus on its regulatory impact on tumor-associated macrophages (TAMs). Our results showed that ESBD inhibited the migration of RAW 264.7 mouse macrophages toward conditioned medium (CM) derived from mouse Lewis lung carcinoma (LLC) cells, which suggests that ESBD might reduce macrophage infiltration into tumor sites. Furthermore, ESBD suppressed the IL-6-induced expression of M2 macrophage markers, including CD206, arginase-1, and IL-10, indicating that ESBD suppresses M2 macrophage polarization in RAW 264.7 cells. Additionally, ESBD decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3), a transcription factor activated by the IL-6 signaling pathway and associated with M2 polarization. Transwell migration assays further showed that CM from M2-polarized RAW 264.7 cells enhanced LLC cell migration, whereas CM from RAW 264.7 cells co-treated with ESBD and IL-6 significantly diminished LLC cell migration. In summary, our findings demonstrate that ESBD attenuates lung cancer cell migration by impairing macrophage recruitment and preventing M2 macrophage polarization.