Abstract
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 ...
Abstract
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 a 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. Conclusion. 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. (c) 2004 Elsevier Inc. All rights reserved.
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