Celecoxib synergizes human pancreatic ductal adenocarcinoma cells to sorafenib-induced growth inhibition |
| |
| Authors: | Ann H. Rosendahl Chinmay Gundewar Katarzyna Said Emelie Karnevi Roland Andersson |
| |
| Affiliation: | 1. Department of Surgery, Clinical Sciences, Lund University, SE-221 84 Lund, Sweden;2. Department of Surgery, Skåne University Hospital Lund, SE-221 85 Lund, Sweden;1. Divisions of Pediatric Cardiology;2. Clinical and Translational Research Organization, All Children’s Hospital/Johns Hopkins Medicine, St Petersburg, Florida;3. Lifelink Immunology Lab, Tampa, Florida;4. Division of Cardiac Surgery, All Children’s Hospital/Johns Hopkins University, St Petersburg, Florida;1. Department of Pharmaceutical Biochemistry, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea;2. Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea;3. Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea;4. Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea;5. Central Research Institute, Boryung Pharm. Co. Ltd, 1122-3, Shingil-Dong, Danwon-Gu, Ansan-Si, Kyungki-Do 425-839, Republic of Korea;1. Division of Cardiothoracic Surgery, Department of Surgery, Columbia University Medical Center, New York, NY;2. Division of Surgery and Epidemiology, Department of Surgery, Columbia University Medical Center, New York, NY;3. Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY;1. Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, The Pancreas Institute, University of Verona Hospital Trust, Italy;2. Unit of Vascular Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Italy;3. Department of Pathology and Diagnostics, University of Verona Hospital Trust, Italy;4. ARC-NET Research Center, University of Verona Hospital Trust, Italy;1. Department of Hepato-Biliary-Pancreatic Surgery, Tochigi Cancer Center, Japan;2. Department of Pathology, Tochigi Cancer Center, Japan |
| |
| Abstract: | BackgroundPancreatic ductal adenocarcinoma is frequently associated with aberrant activation of the Ras/Raf/MAPK pathway and cyclooxygenase-2 (COX-2) overexpression. This study evaluated the potential for combining the multikinase inhibitor sorafenib and the specific COX-2 inhibitor celecoxib as therapy in pancreatic ductal adenocarcinoma cells.MethodsBxPC-3, MIAPaCa-2, PANC-1 and AsPC-1 pancreatic adenocarcinoma cells were exposed to sorafenib and celecoxib combined treatment in vitro. Cell viability and various growth promoting and survival signaling pathways were monitored by MTT, flow cytometry and Western blotting.ResultsCombined treatment with sorafenib and celecoxib synergistically inhibited pancreatic adenocarcinoma cell proliferation. This regimen produced combination index (CI) values between 0.67 and 0.92 for the various cell lines, indicating significant synergistic interactions between sorafenib and celecoxib, which also markedly inhibited the migratory capacity. The growth inhibition was associated with an accumulation of cells in the G0/G1 phase of the cell cycle and induction of apoptosis. These changes were accompanied by a significant reduction of p21WAF1/Cip1 levels, where celecoxib sensitized the cells to sorafenib-mediated p21WAF1/Cip1 suppression.ConclusionThese results suggest that combined treatment with sorafenib and celecoxib synergistically induce growth inhibition and apoptosis in pancreatic adenocarcinoma cells through a process involving p21WAF1/Cip1 suppression. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
