Comparison of the effects of continuous combined and sequential combined medroxyprogesterone acetate–estradiol treatment on the proliferation of MCF-7 cells^*

Abstract

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.

Partly presented at the 2nd Amsterdam Menopause Symposium, Amsterdam, 16–18 April, 2000 and awarded 1st poster prize (abstract BRE 01)

Key Words:

• MEDROXYPROGESTERONE ACETATE
• MCF-7
• CONTINUOUS COMBINED
• SEQUENTIAL COMBINED
• PROLIFERATION