Metformin and 2-Deoxy-d-glucose synergistically inhibit the viability of thyroid papillary carcinoma with BRAF mutation by ROS-dependent PI3K/AKT signaling pathway

The aim of this study was to explore the molecular mechanism through which metformin combined with 2-deoxy-d-glucose (2-DG) decreases the viability of BCPAP thyroid papillary carcinoma cells. BCPAP cells were treated with only metformin, only 2-DG, and both metformin and 2-DG. We used the CCK-8 assay to assess cell viability, dichlorofluorescein staining to detect reactive oxygen species (ROS), and western blot analysis to quantify protein expression. We found that metformin and 2-DG alone decreased cell viability in a time- and dose-dependent manner. The IC50 values of metformin and 2-DG were 5.329 mM and 1.154 mM, respectively. Coadministration of metformin and 2-DG significantly inhibited BCPAP cell proliferation and increased cellular ROS levels and AKT phosphorylation at Ser437. These effects were reversed following the treatment of the cells with N-acetyl-L-cysteine (NAC). Our findings suggest that metformin and 2-DG synergistically suppress BCPAP cell proliferation, potentially via inhibition of the PI3K/AKT signaling pathway by increasing cellular ROS levels.