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Potential role of cyclooxygenase-2 on the regulation of the drug efflux transporter ABCG2 in breast cancer cell lines

Abstract

Purpose

ABCG2 (BCRP) implicated as a member of the multidrug resistance (MDR) proteins in tumors, mediating efflux of a wide spectrum of anticancer drugs. In recent years, there has been an increasing tendency toward the exploring of the potential link between cyclooxygenase-2 (COX-2) expression and development of multidrug resistance phenotype in patients with cancer. The aim of this study was to investigate the role of the COX-2 in modulating drug efflux by ABCG2 in a group of breast cancer cell lines.

Methods

The cytotoxicity of COX-2 inducer (TPA, tetradecanoyl phorbol acetate) and its inhibitor (celecoxib) was determined by an MTT assay. ABCG2 activity was measured by flow cytometric mitoxantrone efflux assay.

Results

TPA exhibited very little inhibitory activity in all cell lines, while long-term treatment with celecoxib significantly inhibited the growth of all cell lines. Furthermore, using mitoxantrone efflux assay was shown that TPA could increase ABCG2 activity in all the cell lines with the greatest stimulatory effects in MCF7-MX (more than 6 times the control level). It seemed that celecoxib inverted the effects of TPA on ABCG2 activity. This was more obvious in MCF7-MX.

Conclusion

The results suggest a probable causal link between COX-2 and ABCG2 activity. The use of celecoxib for adjuvant therapy in cancer treatment may contribute to decreased resistance to chemotherapeutic drugs transported by ABCG2.

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Acknowledgments

The present report has been extracted from the Ph.D. thesis of F. Kalalinia. This study was financially supported by the Research Council of Mashhad University of Medical Sciences, Iran. The authors would like to thank Mr Amir Abbas Azarian (Central Department of Administrative Services, Mashhad University) for his kind assistance with statistical analysis.

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Correspondence to Javad Behravan.

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Kalalinia, F., Elahian, F. & Behravan, J. Potential role of cyclooxygenase-2 on the regulation of the drug efflux transporter ABCG2 in breast cancer cell lines. J Cancer Res Clin Oncol 137, 321–330 (2011). https://doi.org/10.1007/s00432-010-0893-9

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Keywords

  • ABCG2
  • Cyclooxygenase-2
  • Multidrug resistance
  • Celecoxib