The Combined Effect of Canagliflozin and Metformin in Human Prostate Cancer Cells

Abstract

BackgroundThere is still a need to identify effective treatments for castration‐resistant prostate cancers. Recent studies have shown that two drugs used to treat type 2 diabetes, metformin and canagliflozin, may be effective treatments for castration‐resistant prostate cancer. Both drugs have individually been shown to inhibit proliferation of 22Rv1 and PC3 prostate cancer cell lines. However, it is not known if combined treatment with metformin and canagliflozin suppresses the growth of prostate cancer cells better than each drug alone. The goal of this study was to determine the effectiveness of the combination of canagliflozin and metformin as an alternative treatment for prostate cancer.MethodsPresto Blue Assays were used to assess the effect of metformin and canagliflozin on proliferation of the 22Rv1 and PC3 prostate cancer cell lines. Western blot analysis was also performed to determine the effect of metformin and canagliflozin (both individually and combined) on androgen receptor (AR) protein levels. Western blots were stripped and re‐probed for the protein actin to confirm that gels were evenly loaded.ResultsCanagliflozin at a concentration of 30 uM produced a significant decrease in the proliferation of PC3 and 22Rv1 cells. While metformin showed no significant decrease in proliferation of PC3 cells, metformin (5 mM) did significantly decrease 22Rv1 cell proliferation. The combination of canagliflozin and metformin showed a significant decrease in both PC3 and 22Rv1 cells. However, the effect of the combination was no greater than canagliflozin alone. AR protein levels were reduced by canagliflozin, metformin, and the combination of both drugs. Moreover, the combination of metformin and canagliflozin was the most effective in reducing AR protein levels.ConclusionThe combination of canagliflozin and metformin was equally effective as canagliflozin alone at reducing prostate cancer cell proliferation. However, this drug combination was more effective at suppressing AR protein levels within castration‐resistant prostate cancer cells. Taken together, these data suggest that combination treatments involving metformin and canagliflozin could be used to decrease tumor growth and AR expression in prostate cancer patients who have developed castration‐resistant prostate cancer.Support or Funding InformationSupported by NIH grants MD007593 and T34GM007663This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.