Abstract: Objective To investigate the effects of metformin on the proliferation and apoptosis of human oral cancer cell line
KB in vitro. Methods Human oral cancer cell line KB was exposed to different doses of metformin (0, 1.25, 2.5, 5, 10, and 20
mmol/L), and the changes in cell viability were detected using MTT assay. Colony formation of the cells was observed
following an 8-day metformin exposure. The changes in mitochondrial membrane potential were measured by JC-1 assay, and
PI staining was used to observe the cell apoptosis. Western blotting was employed to detect the changes in the protein
expressions of GRP78 and activated caspase-3. Results Metformin exposure caused time- and dose-dependent suppression of
KB cell proliferation, and exposure to 5 mmol/L metformin for 24, 48 and 72 h resulted in cell survival rates of 68.0%, 36.9%,
and 14.5% , respectively. Metformin significantly inhibited KB cell colony formation. Exposure of the cells to increased
concentrations of metformin gradually increased the apoptotic rate and decreased mitochondrial membrane potential.
Metformin caused an initial up-regulation followed by a down-regulation of GRP78 expression in KB cells and increased the
expression of activated caspase-3. Conclusion Metformin can inhibit the proliferation and induce apoptosis of KB cells, the
mechanism of which may involve the activation of the mitochondrial apoptotic pathway and endoplasmic reticulum stress.