Repurposing Doxycycline to Overcome High-Glucose-Induced Mitochondrial Biogenesis-Mediated Chemoresistance in Colorectal Cancer Cells.

ABSTRACT: Chemoresistance is a major contributor to treatment failure in most patients with cancer. Hyperglycaemia enhances chemoresistance in stage III colorectal cancer (CRC) patients, potentially through a mechanism involving c-Myc. Phospho-PGC-1α (p-PGC-1α), a transcription coactivator, regulates energy metabolism with c-Myc and is a key regulator of mitochondrial biogenesis. We hypothesised that high glucose (HG) promotes mitochondrial biogenesis by upregulating c-Myc and p-PGC-1α, thus enhancing chemoresistance in CRC cells, and that inhibiting mitochondrial biogenesis alleviates this chemoresistance. In vitro, HG significantly increased mitochondrial mass (p < 0.001), oxygen consumption rate (p < 0.001), cell migration (p < 0.05) and oxaliplatin resistance (p < 0.001) in LoVo and HCT116 cells

SUBMITTER: Wu CH 

PROVIDER: S-EPMC12516229 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature