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


OBJECTIVE
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 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-kappaB.


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-kappaB activation.
Zatelli
Maria Chiara
MC
Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Ferrara, Italy.
Molè
Daniela
D
Tagliati
Federico
F
Minoia
Mariella
M
Ambrosio
Maria Rosaria
MR
degli Uberti
Ettore
E
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism*; D009578:Nitrobenzenes; D044262:Prostaglandin H2 / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D013449:Sulfonamides; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D044262:Prostaglandin H2; D004317:Doxorubicin; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human