Metformin Induces Various Responses in Caki-1 and Caki-2 Cells

Clear cell renal cell carcinoma (ccRCC) is one of the most common urological cancers diagnosed globally. Two cell lines that derive from human ccRCC are Caki-1 and Caki-2, which express wild-type VHL (von Hippel-Lindau). Defining characteristics of ccRCC include the mutation of the VHL tumor suppressor gene and the overexpression of hypoxia-inducible factor (HIF)-1α protein. Previous studies have suggested that metformin (a drug used to treat diabetes) exhibit antineoplastic effects in different types of cancers since its activation of AMPK evidently decreases the expression of HIF-1α. In this study, researchers analyze the effect of metformin on both Caki-1 and Caki-2 cell lines. Several concentrations of Metformin were used to treat the cell lines, and various assays and analyses were used to observe cell viability, cell cycle arrest, migration, and apoptosis. Results from this study indicate that Metformin inhibited cell growth in both Caki-1 and Caki-2 cell lines. However, Caki-2 appeared to be more sensitive than Caki-1 to Metformin in a dose-dependent manner. Cell cycle analysis revealed that Metformin caused G0/G1 cell cycle arrest in both cell lines, but produced a stronger effect on Caki-2 cells. Metformin failed to induce cytotoxicity or apoptosis in Caki-1 cells, whereas in Caki-2 it produced cytotoxic effects. Cell migration was inhibited by Metformin in both cell lines, and a Western blot analysis further supported its anti-migratory effect by showing the dose-dependent repression of α-SMA protein expression caused by the drug. As a result of Metformin treatment, HIF-1α was expressed more highly in Caki-2 than Caki-1 cells. These findings reveal the complexity of this cancer and how more studies need to be conducted to assure that Metformin is a suitable way to treat ccRCC cell lines. [LINK]