Objectives: The study aims to investigate the mechanisms underlying the anti-cancer effects of losartan in gastric cancer cell line. Methods: In this experimental investigation, MKN-45 cells were cultivated in RPMI-1640 medium supplemented with 10% fetal bovin serum and 100 ?g/ml streptomycinin, and 100 IU/ml penicillin, and maintained under controlled conditions of temperature and CO2. Following washing with PBS, all cells were detached using trypsin, centrifuged and then 8×103 cells re-plated onto 96- well plates. Then various concentrations of Losartan (1000, 2000 and 3000 µM) and 5-fluorouracil (12.5 µM) were added to each well in triple therapy. Anti-proliferative effects of this treatment were evaluated through MTT assay and ROS detection by ROS-sensitive fluorescence indicator after 24 hours. Results: Losartan greatly enhanced the ant-proliferative effect at all tested doses, especially with an IC50 of about 3000 µM in contrast to other groups (P<0.01). Also, cell ROS content due to losartan treatment was significantly reduced compared to untreated group (p<0.05), and the cells treated with Losartan (3000 µM) had considerably lower fluorescence than other groups (p=0.000). Conclusion: In conclusion, this study demonstrated that the various concentration of losartan treatment reduced the viability of MKN-45 gastric cancer cell proliferation, concomitant with a notable decrease in ROS production.
Corresponding Author: Reza Alizadeh-Navaei