Viability Profiles of Normal and Cancer Bladder Cells With Metformin, Nitrate and Adenosine Monophosphate-Activated Protein Kinase Inhibitor.

Background: There is no literature report on how metformin and adenosine monophosphate-activated protein kinase (AMPK) inhibitor affect normal and cancer bladder cells under the presence of nitrate. Methods: Various treatment concentrations and methods were used to study the effects of nitrate, metformin, and/or AMPK inhibitor on normal and/or cancer bladder cells. Normal bladder cells were exposed to nitrate or metformin alone or in combination. The effects of AMPK on normal bladder cells were investigated with nitrate and metformin pretreatment. The effects of varying metformin concentrations on cancer bladder cells were examined as well. Results: Metformin has produced almost no changes in cell viability of normal cells with various concentrations. Addition of both nitrate and metformin at the same time resulted in less than 17% cell viability as compared to the controlled values; however, this value is about 10% better than nitrate alone for 24 h and approximate 27% better for 48 h. Pre-treatment of normal cells with AMPK inhibitor for 6 h prior to addition of metformin and nitrate reduced the cell viability greatly. The treatment of cancer bladder cells with metformin indicated an inverse relationship between metformin concentration and cancer bladder cell viability. Conclusion: Metformin assisted normal bladder cells in surviving in the presence of nitrate, but its total survival was greatly reduced by AMPK inhibitors. Metformin inhibited the growth of bladder cancer cells.