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Article

Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor

  • Authors:
    • Kiyoshi Hasegawa
    • Kunimi Ishikawa
    • Satoshi Kawai
    • Yutaka Torii
    • Kyoko Kawamura
    • Rina Kato
    • Kazuhiko Tsukada
    • Yasuhiro Udagawa
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Fujita Health University, Banbuntane Hotokukai Hospital, Nagoya, Aichi 454‑8509, Japan, Kaseki Hospital, Nagoya, Aichi 460-0008, Japan, Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Nagoya, Aichi 454‑8509, Japan
  • Pages: 2937-2944
    |
    Published online on: October 8, 2013
       https://doi.org/10.3892/or.2013.2790
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Abstract

Cyclooxygenase (COX)-2 inhibitors have been reported to potentially modulate the resistance of cancer cells to chemotherapeutic drugs by affecting multidrug resistance 1 (MDR1) expression. In the present study, we investigated the association between COX-2 and MDR1 expression in endometrial cancers and evaluated the effects of the COX-2 inhibitor, etodolac, in combination with paclitaxel on paclitaxel-resistant endometrial cancer cells. The relationship between COX-2 and MDR1 mRNA expression was examined by quantitative PCR in 36 endometrial cancer specimens. The paclitaxel-resistant cell line OMC-2P was established from OMC-2 cells. Paclitaxel (1 µg/ml) with or without etodolac (10 µg/ml) was added to OMC-2 and OMC-2P cells, and COX-2 and MDR1 mRNA expression levels were examined. The concentration of prostaglandin E2 (PGE2) in the supernatant of each cell line was examined by enzyme-linked immunosorbent assay. The function of MDR1 was determined by intracellular accumulation of rhodamine 123 using flow cytometry, and the concentration of intracellular paclitaxel was determined by high-performance liquid chromatography. We found a positive relationship between COX-2 and MDR1 mRNA expression in endometrial cancer. Both COX-2 mRNA expression and PGE2 production were elevated in resistant OMC-2P cells when compared to non-resistant OMC-2 cells. Additionally, MDR1 mRNA expression was markedly upregulated in OMC-2P cells. In OMC-2 cells, COX-2 and MDR1 mRNA levels were significantly upregulated by paclitaxel treatment and downregulated by co-administration with etodolac. In OMC-2P cells, COX-2 mRNA expression was also significantly upregulated by paclitaxel treatment and tended to be downregulated by co-administration with etodolac. Moreover, co-administration of paclitaxel and etodolac suppressed the induction of MDR1 mRNA. Rhodamine 123 efflux was increased in OMC-2P cells when compared to the efflux in the OMC-2 cells and was increased in response to paclitaxel treatment. Co-administration of paclitaxel and etodolac in both cell lines resulted in decreased rhodamine 123 efflux. The actual concentration of intracellular paclitaxel in OMC-2P cells was significantly lower than that in OMC-2 cells treated with paclitaxel alone and was significantly increased after co-administration of paclitaxel and etodolac. These findings suggest that paclitaxel resistance may be associated with COX-2 and MDR1 expression in cancer cells. Co-administration of COX-2 inhibitors and paclitaxel may have a key role in modulating or overcoming paclitaxel resistance in endometrial cancers.
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Copy and paste a formatted citation
Spandidos Publications style
Hasegawa K, Ishikawa K, Kawai S, Torii Y, Kawamura K, Kato R, Tsukada K and Udagawa Y: Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor. Oncol Rep 30: 2937-2944, 2013.
APA
Hasegawa, K., Ishikawa, K., Kawai, S., Torii, Y., Kawamura, K., Kato, R. ... Udagawa, Y. (2013). Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor. Oncology Reports, 30, 2937-2944. https://doi.org/10.3892/or.2013.2790
MLA
Hasegawa, K., Ishikawa, K., Kawai, S., Torii, Y., Kawamura, K., Kato, R., Tsukada, K., Udagawa, Y."Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor". Oncology Reports 30.6 (2013): 2937-2944.
Chicago
Hasegawa, K., Ishikawa, K., Kawai, S., Torii, Y., Kawamura, K., Kato, R., Tsukada, K., Udagawa, Y."Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor". Oncology Reports 30, no. 6 (2013): 2937-2944. https://doi.org/10.3892/or.2013.2790
Copy and paste a formatted citation
x
Spandidos Publications style
Hasegawa K, Ishikawa K, Kawai S, Torii Y, Kawamura K, Kato R, Tsukada K and Udagawa Y: Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor. Oncol Rep 30: 2937-2944, 2013.
APA
Hasegawa, K., Ishikawa, K., Kawai, S., Torii, Y., Kawamura, K., Kato, R. ... Udagawa, Y. (2013). Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor. Oncology Reports, 30, 2937-2944. https://doi.org/10.3892/or.2013.2790
MLA
Hasegawa, K., Ishikawa, K., Kawai, S., Torii, Y., Kawamura, K., Kato, R., Tsukada, K., Udagawa, Y."Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor". Oncology Reports 30.6 (2013): 2937-2944.
Chicago
Hasegawa, K., Ishikawa, K., Kawai, S., Torii, Y., Kawamura, K., Kato, R., Tsukada, K., Udagawa, Y."Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor". Oncology Reports 30, no. 6 (2013): 2937-2944. https://doi.org/10.3892/or.2013.2790
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