Metformin reduced HIF-1α in colon cancer cells-HCT 116 p53−/− and significantly diminished downstream HIF dependent proteins like VEGF, and carbonic anhydrase 9 (CA9) in these cells, under hypoxic conditions (1.5% O2), however, it slightly increased HIF-1α, VEGF and CA9 under normal O2 concentration (21%)[87]. This evidence concerns the gene VEGFA and colonic neoplasm.