To explore the underlying molecular mechanism(s) involved in the antineoplastic effects of metformin in Caki-1 and Caki-2 cell lines, we investigated the impact of metformin treatment on various crucial signaling pathways involved in the progression of ccRCC: HIF-1α, AMPK, Akt/mTOR and Wnt/β-catenin pathways. This evidence concerns the gene AKT1 and nonpapillary renal cell carcinoma.