SLC5A3 depletion promotes apoptosis by inducing mitochondrial dysfunction and mitophagy in gemcitabine-resistant pancreatic cancer cells.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, largely due to the rapid development of chemoresistance in patients. Mitochondrial dynamics play a crucial role in cancer cell survival. Currently, the specific mechanisms underlying gemcitabine resistance in PDAC remain unknown. In this study, we identified the sodium/myo-inositol co-transporter solute carrier family 5 member 3 (SLC5A3) as a key modulator promoting chemoresistance in PDAC. SLC5A3 levels were significantly upregulated in gemcitabine-resistant PDAC cells, enhancing their cell survival by stabilizing the mitochondrial functions and inhibiting apoptosis. Mitochondrial analysis showed that SLC5A3 inhibition disrupted the mitochondrial dynamics, leading to increased reactive oxygen specie

SUBMITTER: Kim M 

PROVIDER: S-EPMC11889219 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature