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Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress

  • Authors:
    • Jung Lim Kim
    • Dae‑Hee Lee
    • Soyeon Jeong
    • Bo Ram Kim
    • Yoo Jin Na
    • Seong Hye Park
    • Min Jee Jo
    • Yoon A. Jeong
    • Sang Cheul Oh
  • View Affiliations / Copyright

    Affiliations: Division of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, Republic of Korea, Graduate School of Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea
    Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1616-1626
    |
    Published online on: December 19, 2018
       https://doi.org/10.3892/or.2018.6945
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Abstract

Imatinib is a powerful tyrosine kinase inhibitor that specifically targets BCR‑ABL, c‑KIT, and PDGFR kinases, and is used in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and other types of cancers. However, the possible anticancer effects of imatinib in gastric cancer have not yet been explored. The present study evaluated the in vitro effects of imatinib on gastric cancer cells and determined the molecular mechanism underlying these effects. We determined that imatinib induced mitochondria‑mediated apoptosis of gastric cancer cells by involving endoplasmic reticulum (ER) stress‑associated activation of c‑Jun NH2‑terminal kinase (JNK). We also found that imatinib suppressed cell proliferation in a time‑ and dose‑dependent manner. Cell cycle analysis revealed that imatinib‑treated AGS cells were arrested in the G2/M phase of the cell cycle. Moreover, imatinib‑treated cells exhibited increased levels of phosphorylated JNK, and of the transcription factor C/EBP homologous protein, an ER stress‑associated apoptotic molecule. Results of cell viability assays revealed that treatment with a combination of imatinib and chemotherapy agents irinotecan or 5‑Fu synergistically inhibited cell growth, compared with treatment with any of these drugs alone. These data indicated that imatinib exerted cytotoxic effects on gastric cancer cells by inducing apoptosis mediated by reactive oxygen species generation and ER stress‑associated JNK activation. Furthermore, we revealed that imatinib induced the apoptosis of gastric cancer cells by inhibiting platelet‑derived growth factor receptor signaling. Collectively, our results strongly support the use of imatinib in the treatment of treating gastric cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Kim JL, Lee DH, Jeong S, Kim BR, Na YJ, Park SH, Jo MJ, Jeong YA and Oh SC: Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress. Oncol Rep 41: 1616-1626, 2019.
APA
Kim, J.L., Lee, D., Jeong, S., Kim, B.R., Na, Y.J., Park, S.H. ... Oh, S.C. (2019). Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress. Oncology Reports, 41, 1616-1626. https://doi.org/10.3892/or.2018.6945
MLA
Kim, J. L., Lee, D., Jeong, S., Kim, B. R., Na, Y. J., Park, S. H., Jo, M. J., Jeong, Y. A., Oh, S. C."Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress". Oncology Reports 41.3 (2019): 1616-1626.
Chicago
Kim, J. L., Lee, D., Jeong, S., Kim, B. R., Na, Y. J., Park, S. H., Jo, M. J., Jeong, Y. A., Oh, S. C."Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress". Oncology Reports 41, no. 3 (2019): 1616-1626. https://doi.org/10.3892/or.2018.6945
Copy and paste a formatted citation
x
Spandidos Publications style
Kim JL, Lee DH, Jeong S, Kim BR, Na YJ, Park SH, Jo MJ, Jeong YA and Oh SC: Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress. Oncol Rep 41: 1616-1626, 2019.
APA
Kim, J.L., Lee, D., Jeong, S., Kim, B.R., Na, Y.J., Park, S.H. ... Oh, S.C. (2019). Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress. Oncology Reports, 41, 1616-1626. https://doi.org/10.3892/or.2018.6945
MLA
Kim, J. L., Lee, D., Jeong, S., Kim, B. R., Na, Y. J., Park, S. H., Jo, M. J., Jeong, Y. A., Oh, S. C."Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress". Oncology Reports 41.3 (2019): 1616-1626.
Chicago
Kim, J. L., Lee, D., Jeong, S., Kim, B. R., Na, Y. J., Park, S. H., Jo, M. J., Jeong, Y. A., Oh, S. C."Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress". Oncology Reports 41, no. 3 (2019): 1616-1626. https://doi.org/10.3892/or.2018.6945
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