• Sitagliptin enhances the cytotoxic activity of Cisplatin in a bladder cancer cell line HTB-9
  • Shokooh Mohtadi,1 Farnoosh Farzam,2 Shahrzad Molavinia,3 Saeedeh Shariati,4 Masoud Mahdavinia,5 Dian Dayer,6,*
    1. 1 Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 2 Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
    2. Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
    3. 1 Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 2 Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
    4. 1 Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 2 Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
    5. 1 Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 2 Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
    6. Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.


  • Introduction: According to recent research, there seems to be a link between cancer incidence and anti-diabetic drugs. Sitagliptin is a DPP-4 inhibitor that stimulates insulin secretion. Some research found a link between Sitagliptin use and pancreatic cancer progression. However, the impact of Sitagliptin on cancer development is debatable. Other studies have suggested that sitagliptin may have an inhibitory effect on the progression of cancer cells. To address this issue, we looked at the effect of Cisplatin and Sitagliptin combined therapy on the growth and viability of the bladder cancer cell line HTB-9.
  • Methods: The cells were grown in DMEM-HG medium with 10% FBS and 1% Pen/Strep at 37ºC. The IC50 values of sitagliptin and cisplatin were determined using the MTT test. HTB-9 cell lines were incubated with Sitagliptin and/or Cisplatin for 72h. Gene expression was studied using real-time PCR. Protein expression was examined through Western blot.
  • Results: Sitagliptin and cisplatin IC50 values were calculated to be 1545 and 4.2 g/ml, respectively. Treatment of HTB-9 cells with Sitagliptin or Cisplatin in combination or alone resulted in a significant decrease in the expression of proliferation-dependent genes AKT, PI3K, and mTOR compared to the control group. In all treated groups, the noticeable increased expression of Bax was associated with significantly decreased Bcl2 expression. The algorithm for changing the expression of AKT, PI3K, and mTOR, Bax, and BCl2 was similar to that of their dependent genes. The expression of extrinsic and intrinsic apoptotic-related proteins (Caspase 8, Caspase 9, Caspase 3, and Caspase 7) increased significantly after Sitagliptin and/or Cisplatin administration. The group that received a combination of Sitagliptin and Cisplatin had the greatest effect on suppression of proliferation and induction of apoptosis.
  • Conclusion: Sitagliptin enhances Cisplatin's anti-cancer behaviour in HTB-9 cells by suppressing proliferation and increasing apoptosis.
  • Keywords: HT-B-9 cell line, sitagliptin, cisplatin, cytotoxicity