Background: Breast cancer cells can develop chemoresistance after prolonged exposure to cytotoxic drugs due to expression of the multi drug resistance (MDR) 1 gene. Type 2 cyclo-oxygenase (COX-2) inhibitors reverse the chemoresistance phenotype of a medullary thyroid carcinoma cell line, TT, and of a breast cancer cell line, MCF7, by inhibiting MDR1 expression and P-gp function. Aim: investigate the role of prostaglandin (PG) in modulating chemoresistance in MCF7 cells and to explore the involved intracellular mechanisms. Methods: native and chemoresistant MCF7 cells were trated with PGH2 and resistance to Doxorubicin was tested in the presence or absence of COX-2 inhibitors. Results: PGH2 restores resistance to the cytotoxic effects of Doxo, with concomitant nuclear translocation of the transcription factor NF-kB. Conclusions: COX-2 inhibitors prevent chemoresistance development in breast cancer cells by inhibiting P-gp expression and function by a mechanism that involves PGH2 generation and NF-kB activation.

Cyclo-oxygenase 2 modulates chemoresistance in breast cancer cells involving NF-kB.

ZATELLI, Maria Chiara;TAGLIATI, Federico;MINOIA, Mariella;AMBROSIO, Maria Rosaria;DEGLI UBERTI, Ettore
2009

Abstract

Background: Breast cancer cells can develop chemoresistance after prolonged exposure to cytotoxic drugs due to expression of the multi drug resistance (MDR) 1 gene. Type 2 cyclo-oxygenase (COX-2) inhibitors reverse the chemoresistance phenotype of a medullary thyroid carcinoma cell line, TT, and of a breast cancer cell line, MCF7, by inhibiting MDR1 expression and P-gp function. Aim: investigate the role of prostaglandin (PG) in modulating chemoresistance in MCF7 cells and to explore the involved intracellular mechanisms. Methods: native and chemoresistant MCF7 cells were trated with PGH2 and resistance to Doxorubicin was tested in the presence or absence of COX-2 inhibitors. Results: PGH2 restores resistance to the cytotoxic effects of Doxo, with concomitant nuclear translocation of the transcription factor NF-kB. Conclusions: COX-2 inhibitors prevent chemoresistance development in breast cancer cells by inhibiting P-gp expression and function by a mechanism that involves PGH2 generation and NF-kB activation.
2009
Zatelli, Maria Chiara; Molè, D.; Tagliati, Federico; Minoia, Mariella; Ambrosio, Maria Rosaria; DEGLI UBERTI, Ettore
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1378365
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