%0 Journal Article %T Cimetidine and Ibuprofen Modulate T Cell Responses in a Mouse Model of Breast Cancer %J Asian Pacific Journal of Cancer Prevention %I West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter. %Z 1513-7368 %A Oladpour, Omolbanin %A Taghipour, Fereshteh %A Hassan, Zuhair Mohammad %A Rezayati, Mohammad Taghi %A Nemati, Maryam %A Taghipour, Zahra %A Jafarzadeh, Abdollah %D 2022 %\ 06/01/2022 %V 23 %N 6 %P 1847-1858 %! Cimetidine and Ibuprofen Modulate T Cell Responses in a Mouse Model of Breast Cancer %K breast cancer %K Cimetidine %K ibuprofen %K T cells %K Mice %R 10.31557/APJCP.2022.23.6.1847 %X Cimetidine and ibuprofen exhibit immunomodulatory effects as an antagonist of histamine H2 receptor, and a cyclooxygenase inhibitor, respectively. Here, the effects of cimetidine and ibuprofen on some effector T cell-related parameters were investigated using a breast cancer (BC) model. BC was established in Balb/c mice using the 4T1 cell line. On day 10 after tumor induction, the BC-bearing mice were classified into four groups and treated with PBS, cimetidine (20 mg/kg), ibuprofen (20 mg/kg) or a combination of “cimetidine + ibuprofen” via intraperitoneal injection (daily from days 11 to 30). The mice were sacrificed on day 31 and the frequency of splenic Th1 and Treg cells, plasma IFN-γ and TGF-β levels, and intra-tumoral T-bet, GATA3, FOXP3 and RORγt expressions were detected using flowcytometry, ELISA and real-time-PCR, respectively. In untreated cancerous mice, the percentage of splenic Th1 cells and plasma IFN-γ levels were lower (P<0.003 and P<0.01, respectively), whereas the percentage of splenic Treg cells and plasma TGF-β levels were higher than in healthy mice (P<0.04 and P<0.005, respectively). Treatment of BC-bearing mice with cimetidine, ibuprofen or both drugs promoted the frequency of Th1 cells (P<0.05, P<0.007 and P<0.005, respectively) as well as IFN-γ levels (P<0.004, P<0.0001 and P<0.03, respectively), while reduced the frequencies of Treg cells (P<0.02, P<0.03 and P<0.01, respectively), TGF-β levels (P<0.006, P<0.02 and P<0.002, respectively), intra-tumoral expression of FOXP3 (P<0.006, P<0.005 and P<0.005, respectively), and intra-tumoral expression of RORγt (P<0.04, P<0.03 and P<0.05, respectively) compared with untreated BC mice. The “cimetidine + ibuprofen”-treated mice displayed greater T-bet expression than the un-treated mice (P<0.006). Cimetidine and/or ibuprofen-treated BC-bearing mice exhibited reduced intra-tumoral expression of GATA3 compared with the untreated BC mice, but the differences were not significant. Cimetidine and ibuprofen correct some effector T cell-related parameters in cancerous mice. Immunotherapeutic potentials cimetidine and ibuprofen in cancers need investigations.     %U https://journal.waocp.org/article_90138_71a91088d67d7d68aa037a0c25ef9c0e.pdf