Empagliflozin enhances cisplatin activity in chemo-resistant EJ138 bladder cancer cells: The importance of anti-diabetic medications in cancer treatment.

Anti-diabetic medications have been found to reduce chemotherapy resistance. This study sought to investigate the role of Empagliflozin (Empa) as an anti-diabetic medication in reversing Cisplatin (Cis) resistance in EJ138 bladder cancer (BC) cells. The cells were cultured and divided into Cis-treated, Empa-treated, and Cis + Empa-treated cells. The effects of Cis and/or Empa on cell viability were determined using the MTT technique. The levels of ROS produced by cells were evaluated using the green fluorescent dye dichloro-dihydro fluorescein (DCF). The colorimetric method was used to measure Caspase 3/7 activity. The expression of proteins involved in glucose transport, proliferation, apoptosis, cell cycle control, and invasion was evaluated by Western blotting. The IC50 values for Cis and Empa were determined at 16 µM and 160 µM, respectively. ROS generation was significantly elevated after treatment with Cis, Empa, and their combination. Treatment with Cis caused a significant increase in SGLT-2 expression. Conversely, the group treated with Empa showed a significant decrease in SGLT-2 compared with the control group. The combination of Cis and Empa downregulated the expression of SGLT-2, AKT, PI3K, mTOR, Bcl-2, MMP-2, and MMP-9. However, Bax, P21, and P53 expression and caspase 3/7 enzyme activity showed a significant increase following Cis and Empa combination therapy. Empa exhibits beneficial anti-cancer activity against EJ138 cells. Empa boosts SGLT-2 inhibition and anti-cancer activity of Cis in EJ138 BC cancer cells.