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Celecoxib upregulates ULBP‑1 expression in lung cancer cells via the JNK/PI3K signaling pathway and increases susceptibility to natural killer cell cytotoxicity

  • Authors:
    • Jayoung Kim
    • Min Hye Noh
    • Dae Young Hur
    • Bomi Kim
    • Yeong Seok Kim
    • Hyun-Kyung Lee
  • View Affiliations / Copyright

    Affiliations: Department of Medical Science, Pusan National University School of Medicine, Yangsan, South Gyeongsang 50612, Republic of Korea, Department of Anatomy, Inje University College of Medicine, Busan 47396, Republic of Korea, Department of Pathology, Inje University Haewoondae Paik Hospital, Busan 48108, Republic of Korea, Division of Pulmonology, Department of Internal Medicine, Inje University Pusan Paik Hospital, Busan 47396, Republic of Korea
    Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 279
    |
    Published online on: September 23, 2020
       https://doi.org/10.3892/ol.2020.12142
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Abstract

Lung cancer has the highest cancer mortality rate in the world, and effective therapies are still required. Cyclooxygenase‑2 (COX‑2) is highly expressed in numerous types of cancer, and is therefore considered a possible target of cancer treatment. Celecoxib, a selective COX‑2 inhibitor, has binding pockets that interact with COX‑2 and disrupt its enzymatic activities. In addition, celecoxib is able to affect cellular functions in a COX‑2‑independent manner. The present study aimed to investigate if celecoxib affected natural killer (NK) cell receptors and susceptibility to NK cell toxicity. For this purpose, PCR, immunoblotting, flow cytometry analysis and NK cell cytotoxicity assays were performed. The present study revealed that sublethal concentrations of celecoxib increased the expression levels of UL16‑binding protein 1 (ULBP‑1), a natural‑killer group 2 member D (NKG2D) ligand, in lung cancer A549 and H460 cell lines. ULBP‑1 mRNA and protein expression was induced in a dose‑ and time‑dependent manner after celecoxib treatment. Expression levels of other NKG2D ligands, such as ULBP‑2, ULBP‑3, MHC class I‑related chain A (MICA) and MICB did not change considerably compared to ULBP-1 in response to celecoxib treatment. Fluorescence microscopic images revealed abundant ULBP‑1 in the cytoplasm after celecoxib treatment. Both JNK and PI3K may be involved in the induction of ULBP‑1 expression after celecoxib treatment in A549 and H460 cells. In a NK cytotoxicity assay, celecoxib increased the sensitivity to NK cell‑mediated cytotoxicity via interaction with ULBP‑1 in lung cancer cells. Overall, the present results demonstrated that celecoxib treatment induced ULBP‑1 expression in lung cancer cells, thereby increasing their susceptibility to NK cell cytotoxicity. These results suggest that the effects of conventional anticancer therapy may potentially be enhanced by using celecoxib, which targets COX‑2, to enhance the sensitivity of lung cancer cells to NK cell‑mediated cytotoxicity.
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Copy and paste a formatted citation
Spandidos Publications style
Kim J, Noh MH, Hur DY, Kim B, Kim YS and Lee H: Celecoxib upregulates ULBP‑1 expression in lung cancer cells via the JNK/PI3K signaling pathway and increases susceptibility to natural killer cell cytotoxicity. Oncol Lett 20: 279, 2020.
APA
Kim, J., Noh, M.H., Hur, D.Y., Kim, B., Kim, Y.S., & Lee, H. (2020). Celecoxib upregulates ULBP‑1 expression in lung cancer cells via the JNK/PI3K signaling pathway and increases susceptibility to natural killer cell cytotoxicity. Oncology Letters, 20, 279. https://doi.org/10.3892/ol.2020.12142
MLA
Kim, J., Noh, M. H., Hur, D. Y., Kim, B., Kim, Y. S., Lee, H."Celecoxib upregulates ULBP‑1 expression in lung cancer cells via the JNK/PI3K signaling pathway and increases susceptibility to natural killer cell cytotoxicity". Oncology Letters 20.6 (2020): 279.
Chicago
Kim, J., Noh, M. H., Hur, D. Y., Kim, B., Kim, Y. S., Lee, H."Celecoxib upregulates ULBP‑1 expression in lung cancer cells via the JNK/PI3K signaling pathway and increases susceptibility to natural killer cell cytotoxicity". Oncology Letters 20, no. 6 (2020): 279. https://doi.org/10.3892/ol.2020.12142
Copy and paste a formatted citation
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Spandidos Publications style
Kim J, Noh MH, Hur DY, Kim B, Kim YS and Lee H: Celecoxib upregulates ULBP‑1 expression in lung cancer cells via the JNK/PI3K signaling pathway and increases susceptibility to natural killer cell cytotoxicity. Oncol Lett 20: 279, 2020.
APA
Kim, J., Noh, M.H., Hur, D.Y., Kim, B., Kim, Y.S., & Lee, H. (2020). Celecoxib upregulates ULBP‑1 expression in lung cancer cells via the JNK/PI3K signaling pathway and increases susceptibility to natural killer cell cytotoxicity. Oncology Letters, 20, 279. https://doi.org/10.3892/ol.2020.12142
MLA
Kim, J., Noh, M. H., Hur, D. Y., Kim, B., Kim, Y. S., Lee, H."Celecoxib upregulates ULBP‑1 expression in lung cancer cells via the JNK/PI3K signaling pathway and increases susceptibility to natural killer cell cytotoxicity". Oncology Letters 20.6 (2020): 279.
Chicago
Kim, J., Noh, M. H., Hur, D. Y., Kim, B., Kim, Y. S., Lee, H."Celecoxib upregulates ULBP‑1 expression in lung cancer cells via the JNK/PI3K signaling pathway and increases susceptibility to natural killer cell cytotoxicity". Oncology Letters 20, no. 6 (2020): 279. https://doi.org/10.3892/ol.2020.12142
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