Exploring the Effectiveness of Sitagliptin to Enhance Cisplatin Chemosensitivity in HTB‐9 Bladder Cancer Cells

Bladder cancer (BC) is a prevalent malignancy worldwide. Cisplatin (Cis)-based chemotherapy is the principal therapeutic method for many malignancies, including BC. However, side effects and resistance to Cis therapy pose significant challenges in the treatment of BC. Sitagliptin (Sita), an FDA-approved hypoglycemic drug that functions as a DPP-4 inhibitor, has recently received attention in cancer therapy. This study aimed to explore the effects of combined treatment of Cis and Sita on the BC cell line HTB-9. In this study, the IC₅₀ values of Sita and Cis were quantified using an MTT assay. The cells were assigned into four groups: control, Cis, Sita, and Cis + Sita. HTB-9 cells were incubated with Sita and/or Cis for 72 h. Gene expression was assessed via real-time PCR, while protein expression was evaluated by Western blot analysis. The IC₅₀ values for Cis and Sita were 3.01 and 543 μg/ml, respectively. Treatment of HTB-9 cells with Sita or Cis, alone or in combination, led to a significant decline in the mRNA and protein expression of proliferation-dependent markers such as AKT, PI3K, and mTOR. In addition, a notable decrease in mRNA and protein expression of the antiapoptotic marker Bcl-2 was observed in all treated groups. In contrast, the protein expression of proapoptotic markers, including Bax, Caspase-8, Caspase-3, and Caspase-7 increased after treatment with Sita and/or Cis. The findings indicated that the combination treatment with Sita and Cis had the most pronounced effect on suppressing cell proliferation and inducing apoptosis. Overall, it can be suggested that Sita may be a promising candidate for combination therapy with Cis in the treatment of BC.