Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-fluorouracil treatment

  • Authors:
    • Shi Yu Yang
    • Anur Miah
    • Kevin M. Sales
    • Barry Fuller
    • Alexander M. Seifalian
    • Marc Winslet
  • View Affiliations

  • Published online on: March 21, 2011     https://doi.org/10.3892/ijo.2011.982
  • Pages: 1695-1702
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Abstract

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. SB203580 in combination with 5-FU significantly reduced cell viability (P<0.01), and increased cell death and cellular caspase activity (P<0.01). Western blotting data revealed that SB203580 sensitises cancer cells to 5-FU due to an increase in Bax expression. These findings suggest that p38 MAPK is involved in cancer cell survival, and that the inhibition of p38 MAPK can enhance 5-FU to kill colorectal cancer cells.

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June 2011
Volume 38 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yang SY, Miah A, Sales KM, Fuller B, Seifalian AM and Winslet M: Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-fluorouracil treatment. Int J Oncol 38: 1695-1702, 2011.
APA
Yang, S.Y., Miah, A., Sales, K.M., Fuller, B., Seifalian, A.M., & Winslet, M. (2011). Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-fluorouracil treatment. International Journal of Oncology, 38, 1695-1702. https://doi.org/10.3892/ijo.2011.982
MLA
Yang, S. Y., Miah, A., Sales, K. M., Fuller, B., Seifalian, A. M., Winslet, M."Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-fluorouracil treatment". International Journal of Oncology 38.6 (2011): 1695-1702.
Chicago
Yang, S. Y., Miah, A., Sales, K. M., Fuller, B., Seifalian, A. M., Winslet, M."Inhibition of the p38 MAPK pathway sensitises human colon cancer cells to 5-fluorouracil treatment". International Journal of Oncology 38, no. 6 (2011): 1695-1702. https://doi.org/10.3892/ijo.2011.982