Comparison of the effects of continuous combined and sequential combined medroxyprogesterone acetate-estradiol treatment on the proliferation of MCF-7 cells.
OBJECTIVE
The aim of the study was to examine the effects of two different, clinically relevant, hormone replacement therapy (HRT) regimen types, continuous combined and sequential combined, on breast cancer cells by means of an in vitro model. The study was carried out using the C21-progestin medroxyprogesterone acetate (MPA) in combination with estradiol, and with the proliferation of MCF-7, a human breast cancer cell-line, as end-point.


METHODS
Proliferation of MCF-7 cells was measured by means of a crystal violet staining technique. Growth was triggered using a constant estradiol concentration of 10(-10) mol/l, while varying the MPA concentration from 10(-11) to 10(-6) mol/l.


RESULTS
The continuous combined model of treatment led to the inhibition of estradiol-induced growth of MCF-7 with MPA concentrations of 10(-10) mol/l and upwards, compared with estradiol-alone-induced growth. The sequential combined model showed a greater inhibition at the higher MPA concentrations of 10(-8)-10(-6) mol/l, with reduced sensitivity to inhibition at the lower MPA concentrations tested, of 10(-11)-10(-9) mol/l. The different treatment types resulted in significantly different sensitivities of the MCF-7 cells to inhibition of estradiol-induced proliferation at the higher MPA concentrations of 10(-8)-10(-6) mol/l.


CONCLUSIONS
The results demonstrate the importance of considering in vivo factors in an in vitro model with regard to improving the cell culture techniques used, to obtain a clearer picture of the possible mechanisms involved in the potential breast cancer risk with different HRT regimens.
Lippert
C
C
Section of Endocrinology and Menopause, Department of Obstetrics and Gynecology, University of Tuebingen, Schleichstr. 4, 72076 Tuebingen, Germany.
Seeger
H
H
Wallwiener
D
D
Mueck
A O
AO
D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004958:Estradiol; D017258:Medroxyprogesterone Acetate