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Article

Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin treatment in vitro and in vivo

  • Authors:
    • Wei Tan
    • Hong-Gang Yu
    • He-Sheng Luo
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Wuhan University, Renmin Hospital, Wuhan, Hubei 430060, P.R. China, Institute for Gastroenterology and Hepatology, Wuhan University Medical School, Wuhan, Hubei 430060, P.R. China
  • Pages: 3275-3281
    |
    Published online on: September 25, 2014
       https://doi.org/10.3892/mmr.2014.2598
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Abstract

Gastric cancer is the second most common cause of cancer-related deaths worldwide. Doxorubicin-based chemotherapeutic regimes have been the mainstay of systemic treatment for disseminated gastric cancer for numerous years. However, the efficacy of doxorubicin is severely limited due to chemoresistance. Chemoresistance is a tightly regulated process, under the control of numerous signal transduction pathways. Amongst these, the mitogen-activated protein kinase (MAPK) pathway has received much attention. This study assessed whether the p38 MAPK pathway is involved in doxorubicin resistance in gastric cancer cells. Doxorubicin alone or combined with the p38 MAPK pathway inhibitor SB203580 was used to treat gastric cancer cells (SGC7901 and BGC823 lines). The effect of doxorubicin on the growth and apoptosis of gastric cancer cells in the presence or absence of SB203580 was investigated by western blot analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst staining, Annexin V-FITC/propidium iodide staining followed by flow cytometry analysis, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Next, the effects of doxorubicin and SB203580, on the sensitivity of BGC-823 cells were assessed in a tumor xenograft model. The results showed that the p38 MAPK inhibitor significantly increases gastric cancer cell sensitivity to doxorubicin. Doxorubicin in combination with SB203580 significantly reduced cell viability (P<0.01) and increased cell death (P<0.01), which may be associated with the inactivation of the p38 MAPK signaling pathway, followed by the induced expression of the pro-apoptotic protein Bax and a concomitant decrease in Bcl-2 expression. These findings suggest that p38 MAPK is involved in gastric cancer cell survival, and that the inhibition of p38 MAPK signaling can reduce the tolerance of gastric cancer cells to doxorubicin treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Tan W, Yu H and Luo H: Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin treatment in vitro and in vivo. Mol Med Rep 10: 3275-3281, 2014.
APA
Tan, W., Yu, H., & Luo, H. (2014). Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin treatment in vitro and in vivo. Molecular Medicine Reports, 10, 3275-3281. https://doi.org/10.3892/mmr.2014.2598
MLA
Tan, W., Yu, H., Luo, H."Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin treatment in vitro and in vivo". Molecular Medicine Reports 10.6 (2014): 3275-3281.
Chicago
Tan, W., Yu, H., Luo, H."Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin treatment in vitro and in vivo". Molecular Medicine Reports 10, no. 6 (2014): 3275-3281. https://doi.org/10.3892/mmr.2014.2598
Copy and paste a formatted citation
x
Spandidos Publications style
Tan W, Yu H and Luo H: Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin treatment in vitro and in vivo. Mol Med Rep 10: 3275-3281, 2014.
APA
Tan, W., Yu, H., & Luo, H. (2014). Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin treatment in vitro and in vivo. Molecular Medicine Reports, 10, 3275-3281. https://doi.org/10.3892/mmr.2014.2598
MLA
Tan, W., Yu, H., Luo, H."Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin treatment in vitro and in vivo". Molecular Medicine Reports 10.6 (2014): 3275-3281.
Chicago
Tan, W., Yu, H., Luo, H."Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin treatment in vitro and in vivo". Molecular Medicine Reports 10, no. 6 (2014): 3275-3281. https://doi.org/10.3892/mmr.2014.2598
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