Dauricine Inhibits Macrophages M2 Polarization and Regulates the Progression and Ferroptosis via HCK/IDO1 in Urinary Bladder Cancer

ABSTRACT Tumor‐associated macrophages (TAMs), particularly the M2 phenotype, have the ability to promote malignant tumor progression and metastasis. Dauricine (DAU) is a Chinese herbal monomer that has been shown to have inhibitory effects on various tumor cells. However, the mechanisms by which DAU influences tumor microenvironment and bladder cancer (BLCA) progression remain unclear. Herein, we investigated the effects of DAU on macrophage M2 polarization and BLCA progression. In this study, besides demonstrating that DAU can mediate the inhibition of macrophage M2 polarization and promote macrophage ferroptosis induced by BLCA cell supernatants via HCK, we further verified that DAU regulated IDO1, which is downstream of HCK, to affect the M2‐like TAMs induced by BLCA progression and ferroptosis. In addition, we also observed an increase in ferritinophagy in BLCA cells under DAU treatment. These findings reveal an unsuspected function of DAU in inhibiting malignant progression of BLCA by interfering with M2 polarization and ferroptosis in TAMs through the HCK/IDO1 axis.