When combined with LY294002 (an inhibitor of the PI3K/AKT/mTOR pathway with anti-angiogenic properties), metformin showed a marked reduction in viability and tumor cell growth in vitro, while in CMC xenografted mice, both drugs decreased the tumor size and showed an important anti-angiogenic effect (reduction of VEGF-A expression and MVD) (275). Here, VEGFA is linked to neoplasm.