The effects of estrogen, progesterone, and tamoxifen alone and in combination with cytotoxic agents against human ovarian carcinoma in vitro.
The effects of estradiol (E), medroxyprogesterone acetate (MPA), and tamoxifen (TAM) on the growth of a human ovarian carcinoma cell line, BG-1, were evaluated using a tumor clonogenic assay (HTCA). BG-1 contains significant quantities of estrogen and progesterone receptors. Growth inhibition by TAM and growth stimulation by MPA were demonstrated using continuous drug exposure. Estradiol resulted in a marginal increase in colony formation. With each of these three drugs, the greatest response occurred in the larger colonies (generally greater than or equal to 60 microns). Combinations of each of these three steroidal agents with three different cytotoxic drugs were studied in the HTCA. Synergistic activities were produced with TAM combined with either cisplatin or doxorubicin. Additive effects were seen with TAM and cyclophosphamide. Although predominantly additive or synergistic, the effects were variable with MPA and all three cytotoxic agents. Combinations of estradiol with cytotoxic agents were no more active than the cytotoxics alone. These findings indicate a biological rationale for hormonal manipulation as therapy in ovarian cancer.
Geisinger
K R
KR
Department of Pathology, Wake Forest University, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103.
Berens
M E
ME
Duckett
Y
Y
Morgan
T M
TM
Kute
T E
TE
Welander
C E
CE
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004347:Drug Interactions; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017258:Medroxyprogesterone Acetate; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013629:Tamoxifen / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D013629:Tamoxifen; D004958:Estradiol; D004317:Doxorubicin; D003520:Cyclophosphamide; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone