Effect of antiprogestins and tamoxifen on growth inhibition of MCF-7 human breast cancer cells in nude mice.
This is the first report demonstrating an in vivo antitumor activity of antiprogestins (mifepristone, onapristone) alone and in combination with tamoxifen in the MCF-7 human breast cancer model. The MCF-7 cells produced progressive growing tumors in female nude mice supplemented with 17beta-estradiol. Tumor regression was observed following either estrogen ablation alone or estrogen ablation in combination with tamoxifen. Monotherapy with tamoxifen or antiprogestins caused a retardation of estrogen-induced tumor progression. Complete inhibition or prevention of tumor growth occurred as a result of simultaneous administration of mifepristone and tamoxifen. The addition of mifepristone in this combination treatment was also effective in delaying or preventing tumor escape (relapse) from the antiestrogenic (antitumor) effect of tamoxifen. These results suggest a potential clinical benefit of adding an antiprogestin to antiestrogen therapy of breast cancer patients.
Department of Surgery, Medical College of Georgia, Augusta 30912, USA.
M F
MF
El Etreby
Y
Y
Liang
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006067:Gonanes / Q000627:therapeutic use*; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015735:Mifepristone / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000187:drug effects; D011980:Receptors, Progesterone; D013629:Tamoxifen / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D006067:Gonanes; D006727:Hormone Antagonists; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D015735:Mifepristone; C053238:onapristone