Effects of prolonged tamoxifen treatment on receptor expression and apoptosis of ovarian cancer cells.
OBJECTIVE
Tamoxifen, which is widely used in the treatment of breast cancer, also has a beneficial effect on cisplatin-refractory ovarian cancer. In this study, we investigated the long-term effects of this drug on estrogen-receptor-positive ovarian cancer cells.


METHODS
We performed an in vitro selection process by long-term treatment of BG-1 ovarian cancer cells with 4-hydroxy tamoxifen (4-OH TAM). Drug effects on cell growth were determined by measurement of relative cell numbers (MTS assay), the apoptotic effects of 4-OH TAM were determined by analysis of poly (ADP-ribose) polymerase (PARP) cleavage and by ELISA measurement of DNA-histone complexes in cytoplasm.


RESULTS
Analysis of BG-1(LT) ovarian cancer cells isolated after 5 months of long-term treatment with 4-OH TAM revealed both a significantly reduced apoptotic and antiproliferative effect of this drug. Further experiments to examine expression changes of the receptor tyrosine kinases EGFR, HER2 and estrogen receptor alpha did not reveal any alterations in BG-1(LT) if compared to wild-type cells. In contrast, in this cell line, a significant alteration in the expression of estrogen receptor beta was observed.


CONCLUSIONS
Our findings indicate that long-term treatment with 4-OH TAM is able to diminish both the antiproliferative and apoptotic action of this drug on BG-1 ovarian cancer cells. Our data suggest that the responsiveness of ovarian cancer cells to 4-OH TAM decreases after long-term treatment with this drug in vitro like previously observed after long-term treatment of breast cancer cells.
Zhou
Rong
R
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, 610041 Chengdu, PR China.
Treeck
Oliver
O
Horn
Felicitas
F
Ortmann
Olaf
O
D017209:Apoptosis / Q000187:drug effects*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000096:biosynthesis; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*
D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011065:Poly(ADP-ribose) Polymerases; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene