Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-fluorouracil treatment
| Autor: | Anur Miah, Alexander M. Seifalian, Barry Fuller, Kevin M. Sales, Shi Yu Yang, Marc C. Winslet |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
MAPK/ERK pathway
Antimetabolites Antineoplastic Cancer Research Cell Survival Colorectal cancer Mouse model of colorectal and intestinal cancer p38 Mitogen-Activated Protein Kinases Cell Line Tumor Humans Medicine Viability assay Protein Kinase Inhibitors bcl-2-Associated X Protein Cell Death Oncogene business.industry Cancer HCT116 Cells medicine.disease Enzyme Activation Proto-Oncogene Proteins c-bcl-2 Oncology Apoptosis Caspases Colonic Neoplasms Immunology Cancer cell Cancer research Fluorouracil business HT29 Cells Signal Transduction |
| Zdroj: | International Journal of Oncology. |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2011.982 |
| Popis: | Colorectal cancer is the third most common cause of cancer-related deaths in the Western world. 5-Fluorouracil (5-FU) based chemotherapeutic regimes have been the mainstay of systemic treatment for disseminated colorectal cancer for many years. However, it only produces a 25% response rate due to the drug-resistance. The mitogen-activated protein kinase (MAPK) pathway is involved in the anti-apoptotic process; its activation provides cancer cells with a survival advantage to escape the apoptotic challenge. This study assessed whether the p38 MAPK pathway is involved in 5-FU resistance in colorectal cancer cells. 5-FU only or 5-FU combined with a p38 MAPK pathway inhibitor (SB203580) was used to treat 5-FU-resistant colorectal cancer cells. The effect of the treatment on cell viability, death and caspase activities was assessed. Western blotting was used to investigate the responses of apoptosis-related proteins following the treatment. Results showed that p38 MAPK inhibitor significantly increased colorectal cancer cell sensitivity to 5-FU. 513203580 in combination with 5-FU significantly reduced cell viability (P |
| Databáze: | OpenAIRE |
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