Open AccessCyclo-Oxygenase 2 Modulates Chemoresistance in Breast Cancer Cells Involving NF-κB
Author(s) -
Maria Chiara Zatelli,
Daniela Molè,
Federico Tagliati,
Mariella Minoia,
Maria Rosaria Ambrosio,
Ettore Degli Uberti
Publication year - 2009
Publication title -
analytical cellular pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.576
H-Index - 24
eISSN - 2210-7185
pISSN - 2210-7177
DOI - 10.1155/2009/658524
Subject(s) - cytotoxic t cell , cancer research , cancer cell , doxorubicin , cell culture , transcription factor , breast cancer , nf κb , cancer , intracellular , downregulation and upregulation , multiple drug resistance , medicine , biology , drug resistance , chemotherapy , in vitro , gene , microbiology and biotechnology , inflammation , biochemistry , genetics
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 treated with PGH 2 and resistance to Doxorubicin was tested in the presence or absence of COX-2 inhibitors. Results : PGH 2 restores resistance to the cytotoxic effects of Doxo, with concomitant nuclear translocation of the transcription factor NF-κB. Conclusions : COX-2 inhibitors prevent chemoresistance development in breast cancer cells by inhibiting P-gp expression and function by a mechanism that involves PGH 2 generation and NF- κ B activation.