A CD147-targeted small-molecule inhibitor potentiates gemcitabine efficacy by triggering ferroptosis in pancreatic ductal adenocarcinoma.

ABSTRACT: CD147 has emerged as a promising tumor-specific therapeutic target. Identifying small-molecule inhibitors that promote its proteolysis represents a critical step toward advancing clinical translation, while elucidating its mechanisms of action could further accelerate this process. In this study, we identify dracorhodin perchlorate (DP) as a potent CD147 inhibitor that induces autophagy-dependent degradation. DP significantly inhibits cell proliferation and enhances sensitivity to gemcitabine in pancreatic cancer cells. Mechanistically, 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

SUBMITTER: Li J 

PROVIDER: S-EPMC12432379 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature