A synergistic AMPK-dependent sensitization, enhancement of anti-proliferative effect, and activation of apoptosis was observed in parental MDA-MB-468, MDA-MB-231, and SKBR3 breast cancer cells when metformin (2.5 mM to 20 mM) was used in combination with 5-FU, epirubicin, and cyclophosphamide (FEC) [127]. This evidence concerns the gene PRKAA2 and breast cancer.