RESUMEN
Prostate cancer (PCa) ranks as the sixth most serious male malignant disease globally. While docetaxel (DTX) chemotherapy is the standard treatment for advanced PCa patients with distant metastasis, some individuals exhibit insensitivity or resistance to DTX. Cancer-associated fibroblasts (CAFs) play a pivotal role as stromal cells within the tumor microenvironment, influencing tumor development, progression, and drug resistance through exosomes. Ferroptosis, a novel form of programmed cell death, is characterized by intracellular iron accumulation that triggers lipid peroxidation, ultimately leading to cell demise. To delve into the potential mechanisms of chemotherapy resistance in prostate cancer, our research delved into the impact of CAF-derived exosomes on ferroptosis. Our findings revealed that CAF exosomes hindered the buildup of lipid reactive oxygen species (ROS) in prostate cancer cells induced by erastin, as well as mitigated erastin-induced mitochondrial damage, thereby impeding iron-induced cell death in prostate cancer cells. Furthermore, miR-432-5p was identified to diminish glutathione (GSH) consumption by targeting CHAC1, consequently inhibiting ferroptosis in prostate cancer cells. Our study found that miR-432-5p, originating from cancer-associated fibroblast (CAF) exosomes, suppresses ferroptosis by targeting CHAC1, thereby increasing resistance to docetaxel (DTX) in PCa. This research introduces a novel approach to address resistance to DTX.