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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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2014-February Volume 44 Issue 2

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International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

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Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

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World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

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International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

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International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

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Article

Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate

  • Authors:
    • Onika T. Murray
    • Chi C. Wong
    • Kvetoslava Vrankova
    • Basil Rigas
  • View Affiliations / Copyright

    Affiliations: Division of Cancer Prevention, Department of Medicine, Stony Brook University, Stony Brook, NY 11794-8173, USA
  • Pages: 521-529
    |
    Published online on: November 27, 2013
       https://doi.org/10.3892/ijo.2013.2190
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Abstract

Phospho-sulindac (P-S), a promising anticancer agent, is efficacious in pre-clinical models of human cancer and is apparently safe. Here, we studied the effect of P-S on pancreatic cancer growth. We found that P-S strongly inhibits the growth of human pancreatic cancer cells in vitro, is efficacious in inhibiting the growth of pancreatic xenografts in nude mice, and has an excellent safety profile. Microarray analysis revealed that P-S induced the expression of nuclear factor of activated T-cells, isoform c1 (NFATc1) gene. NFATc1, a calcineurin-responsive transcription factor associated with aggressive pancreatic cancer. The role of increased NFATc1 expression on the growth inhibitory effect of P-S on cancer growth was evaluated by silencing or by overexpressing it both in vitro and in vivo. We found that when the expression of NFATc1 was abrogated by RNAi, pancreatic cancer cells were more responsive to treatment with P-S. Conversely, overexpressing the NFATc1 gene made the pancreatic cancer cells less responsive to treatment with P-S. NFATc1 likely mediates drug resistance to P-S and is an unfavorable prognostic factor that predicts poor tumor response. We also demonstrated that NFATc1-mediated resistance can be overcome by cyclosporin A (CsA), an NFAT inhibitor, and that the combination of P-S and CsA synergistically inhibited pancreatic cancer cell growth. In conclusion, our preclinical data establish P-S as an efficacious drug for pancreatic cancer in preclinical models, which merits further evaluation.
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Copy and paste a formatted citation
Spandidos Publications style
Murray OT, Wong CC, Vrankova K and Rigas B: Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate. Int J Oncol 44: 521-529, 2014.
APA
Murray, O.T., Wong, C.C., Vrankova, K., & Rigas, B. (2014). Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate. International Journal of Oncology, 44, 521-529. https://doi.org/10.3892/ijo.2013.2190
MLA
Murray, O. T., Wong, C. C., Vrankova, K., Rigas, B."Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate". International Journal of Oncology 44.2 (2014): 521-529.
Chicago
Murray, O. T., Wong, C. C., Vrankova, K., Rigas, B."Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate". International Journal of Oncology 44, no. 2 (2014): 521-529. https://doi.org/10.3892/ijo.2013.2190
Copy and paste a formatted citation
x
Spandidos Publications style
Murray OT, Wong CC, Vrankova K and Rigas B: Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate. Int J Oncol 44: 521-529, 2014.
APA
Murray, O.T., Wong, C.C., Vrankova, K., & Rigas, B. (2014). Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate. International Journal of Oncology, 44, 521-529. https://doi.org/10.3892/ijo.2013.2190
MLA
Murray, O. T., Wong, C. C., Vrankova, K., Rigas, B."Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate". International Journal of Oncology 44.2 (2014): 521-529.
Chicago
Murray, O. T., Wong, C. C., Vrankova, K., Rigas, B."Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate". International Journal of Oncology 44, no. 2 (2014): 521-529. https://doi.org/10.3892/ijo.2013.2190
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