Synergistic antiproliferative activity of tamoxifen and cisplatin on primary ovarian tumours.
We looked for the presence of the so-called type II oestrogen binding sites (EBS), in four oestrogen (ER) and progesterone (PR) receptor negative primary ovarian tumours. Moreover, the colony-forming assay was used to evaluate the response of ovarian cancer cells from these primary tumours to tamoxifen and cisplatin used alone or in combination. All tumours contained type II EBS, and tamoxifen was able to compete for [3H] oestradiol binding to these sites. Cisplatin and tamoxifen exhibited a dose-dependent inhibition of colony formation in a range of concentrations between 10 and 1000 micrograms/l and 37 and 3710 micrograms/l, respectively. The combination of the two drugs resulted in a synergistic antiproliferative activity, with a potentiation up to and beyond 50-fold. Our results show that in ovarian cancer tamoxifen interacts with type II EBS with an affinity consistent with the concentration effective both in inhibition of colony formation and in synergising cisplatin activity. Based on the experiments performed the action of tamoxifen on cell growth is independent of ER expression, and could be mediated by type II EBS. The possibility that the association of tamoxifen and cisplatin may result in an improved clinical response in ovarian cancer should be investigated.
Scambia
G
G
Department of Gynecology, Catholic University, Milan, Italy.
Ranelletti
F O
FO
Benedetti Panici
P
P
Piantelli
M
M
De Vincenzo
R
R
Bonanno
G
G
Ferrandina
G
G
Isola
G
G
Mancuso
S
S
D001665:Binding Sites; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D004967:Estrogens; D011960:Receptors, Estrogen; D013629:Tamoxifen; D002945:Cisplatin