Is there a protective role of progestogens on the proliferation of human ovarian cancer cells in the presence of growth factors?
OBJECTIVE
The role of progestogens in the genesis of ovarian cancer remains unclear although a rather protective behaviour has been suggested. Epidemiological studies indicate a possible increase in the risk for combined estrogen/progestin as compared to estrogen alone. It is ambigious whether a difference exists within the various progestogens. Apart from sex steroids, growth factors play a crucial role in the genesis of ovarian cancer, although as yet little investigated. In the present study we have explored the effect of progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) on the proliferation of human ovarian cancer cells alone and in the presence of growth factors.


METHODS
For the experiments human ovarian cancer cells (OVCAR-3) were used. The progestogens were tested at the concentrations of 0.01 to 10 microM. The growth factor mixture consisted of EGF, FGF and IGF-I, each at a concentration of 10 pM. The incubation time was three or seven days. Proliferation rate was measured by an ATP-assay.


RESULTS
After three days' incubation the growth factors induced an increase in the proliferation rate of about 50%. Progesterone alone did not show any significant change as compared to the control values, whereas NET and MPA elicited a significant increase at 1 and 10 microM and at 1 microM, respectively. In the presence of growth factors none of the progestogens was able to inhibit the proliferative stimulation. After seven days' incubation the growth factors still showed an increase of about 50%. MPA alone had an inhibitory effect at 10 microM, for NET and P no effects were observed. Again in the presence of growth factors no progestogen was able to show an inhibitory effect.


CONCLUSIONS
Our results indicate that progestogens do not have a protective role on the growth of pre-existing ovarian cancer cells, at least in the presence of growth factors. Further investigations are worthwile to evaluate possible differences between the effect of the various progestogens.
Seeger
H
H
Section of Endocrinology and Menopause, University Women's Hospital, Tuebingen, Germany.
Wallwiener
D
D
Mueck
A O
AO
D000704:Analysis of Variance; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018969:Insulin-Like Growth Factor Binding Proteins / Q000494:pharmacology*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D009640:Norethindrone / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011372:Progestins / Q000494:pharmacology*; D020011:Protective Agents
D018931:Antineoplastic Agents, Hormonal; D018969:Insulin-Like Growth Factor Binding Proteins; D011372:Progestins; D020011:Protective Agents; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone