Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2023 , Vol 27 , Issue 2
Imatinib Synergizes with 2, 5- Dimethylcelecoxib, a Close Derivative of Celecoxib, in HT-29 Colorectal Cancer Cells: Involvement of Vascular Endothelial Growth Factor
1Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
3Department of Biochemistry, Faculty of Medicine, Solid Tumor and Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
4Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
DOI : 10.29228/jrp.374 Combining agents with molecular targets can reduce monotherapy’s required dose and toxicity in cancer treatment. In this study, we investigated the cellular viability and the mRNA expression of vascular endothelial growth factor (VEGF) and nuclear factor kappa B (NF-κB) for the synergistic effects of imatinib and 2, 5- dimethylcelecoxib (DMC) combination in human colorectal cancer cells. The effects of imatinib and DMC on cell viability were assessed by MTT assay in HT-29 cells. The dose-effect relationships and drug interaction analyses were performed using the CompuSyn Software. NF-κB and VEGF mRNA expression after treating cells with imatinib (7 μM) and DMC (24 μM) separately and in combination (3.5 μM imatinib plus 12 μM DMC) were investigated using real-time RT-PCR. A strong synergy was observed in most of the combined dose pairs of imatinib- DMC in the growth inhibition of HT-29 cancer cells. Combined treatment with 3.5 μM imatinib and 12 μM DMC resulted in a significant (p ˂ 0.05) decrease in VEGF and NF-κB mRNA levels as compared to the vehicle-treated control group. In addition, VEGF mRNA reduction was significant at the mentioned concentrations for the imatinib-DMC combination compared to imatinib alone (p ˂ 0.05). Our results suggest VEGF as one of the cyclooxygenase2 (COX-2) independent mechanisms for the synergistic effects of imatinib-DMC. It would be beneficial to further evaluate the potential utilization of DMC for the anti-cancer application while minimizing undesired side effects related to COX-2 inhibition and reducing the side effects of imatinib therapy. Keywords : Colorectal cancer; Cyclooxygenase 2; 2,5-dimethylcelecoxib; NF-kappa B
Marmara University