Reversal of P-glycoprotein-mediated multidrug resistance in human sarcoma MES-SA/Dx-5 cells by nonsteroidal anti-inflammatory drugs

  • Authors:
    • Antonio Angelini
    • Manuela Iezzi
    • Concetta Di Febbo
    • Carmine Di Ilio
    • Franco Cuccurullo
    • Ettore Porreca
  • View Affiliations

  • Published online on: October 1, 2008     https://doi.org/10.3892/or_00000067
  • Pages:731-735
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Abstract

Multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) is one of the major reasons for the failure of cancer therapy. Several chemosensitizers are able to reverse in vitro MDR by inhibiting P-gp, although high toxicity limits their clinical application. In this study, we aimed to investigate the in vitro effectiveness of four common non-steroidal anti-inflammatory drugs (NSAIDs) such as Curcumin (Cur), Sulindac (Sul), Ibuprofen (Ibu) and NS-398 (NS) to inhibit P-gp activity at clinically achievable doses and to evaluate their potential use as sensitizers in anti-cancer chemotherapy. The human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx-5) expressing high levels of P-gp, were treated with different doxo concentrations in the presence or absence of NSAIDs. Cellular accumulation of doxo, cytotoxicity and apoptosis induction were measured in comparison with Verapamil, a specific P-gp inhibitor, used as a reference molecule. We found that Ibu, Cur and NS-398 enhanced significantly doxo retention, cytotoxicity and apoptosis on resistant MES-SA/Doxo-5 cells when compared with doxo alone. In contrast, no significant changes were found in resistant cells treated with Sul-doxo combinations. Our results demonstrate that Ibu, Cur and NS-398 below their therapeutic plasma concentrations were able to overcome P-gp-mediated MDR in MES-SA/Dx-5 cells. These findings provide the rationale for clinical studies of NSAIDs and/or derivatives as a new potential generation of chemosensitizers to improve effectiveness of the anti-cancer drugs in the treatment of human cancer.

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October 2008
Volume 20 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

2015 Impact Factor: 2.486
Ranked #31/211 Oncology
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APA
Angelini, A., Iezzi, M., Di Febbo, C., Di Ilio, C., Cuccurullo, F., & Porreca, E. (2008). Reversal of P-glycoprotein-mediated multidrug resistance in human sarcoma MES-SA/Dx-5 cells by nonsteroidal anti-inflammatory drugs. Oncology Reports, 20, 731-735. https://doi.org/10.3892/or_00000067
MLA
Angelini, A., Iezzi, M., Di Febbo, C., Di Ilio, C., Cuccurullo, F., Porreca, E."Reversal of P-glycoprotein-mediated multidrug resistance in human sarcoma MES-SA/Dx-5 cells by nonsteroidal anti-inflammatory drugs". Oncology Reports 20.4 (2008): 731-735.
Chicago
Angelini, A., Iezzi, M., Di Febbo, C., Di Ilio, C., Cuccurullo, F., Porreca, E."Reversal of P-glycoprotein-mediated multidrug resistance in human sarcoma MES-SA/Dx-5 cells by nonsteroidal anti-inflammatory drugs". Oncology Reports 20, no. 4 (2008): 731-735. https://doi.org/10.3892/or_00000067