Dracorhodin perchlorate is a potent CD147 inhibitor that induces autophagy-dependent degradation, triggers PUFA/MUFA balance-mediated ferroptosis. Dracorhodin perchlorate significantly inhibits cell proliferation and enhances sensitivity to gemcitabine in pancreatic cancer cells. CD147 inhibition upregulates acyl-CoA synthetase long-chain family member 4 (ACSL4) expression through H3K9 lactylation and suppresses the sterol regulatory element-binding protein 1 (SREBP1)/stearoyl-CoA desaturase-1 (SCD1) signaling pathway, collectively disrupting the balance of polyunsaturated and monounsaturated fatty acids, ultimately triggering ferroptosis. The combination of Dracorhodin and gemcitabine demonstrates remarkable synergistic anti-tumor effects in orthotopic xenograft models, spontaneous KPC mouse models, and patient-derived organoid (PDO) and xenograft (PDX) models.
