Growth inhibition of mouse MXT mammary tumor by the luteinizing hormone-releasing hormone antagonist SB-75.
Female BDF1 mice bearing MXT mammary adenocarcinomas were treated for 3 weeks with the luteinizing hormone-releasing hormone (LH-RH) antagonist [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]-LH-RH (SB-75), with the agonist D-Trp6-LH-RH, with tamoxifen (5 micrograms per animal per day subcutaneously), with the combination of D-Trp6-LH-RH and tamoxifen, or by surgical ovariectomy. SB-75 and D-Trp6-LH-RH were administered in the form of microcapsules releasing 25 micrograms/day. The reduction in tumor weights after treatment with SB-75, D-Trp6-LH-RH, D-Trp6-LH-RH plus tamoxifen, or ovariectomy was 84%, 64%, 33%, and 67%, respectively. Tamoxifen alone was ineffective. Histologically, the regressive changes in the treated tumors were characteristic of apoptosis (programmed cell death). In view of its potency and its immediate inhibitory effect, the LH-RH antagonist SB-75 should be considered as a possible new hormonal agent for the treatment of breast cancer.
Szende
B
B
Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, LA 70146.
Srkalovic
G
G
Groot
K
K
Lapis
K
K
Schally
A V
AV
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents; D001835:Body Weight / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D017451:Receptors, Somatomedin
D000970:Antineoplastic Agents; D011956:Receptors, Cell Surface; D011974:Receptors, LH; D017451:Receptors, Somatomedin; D007987:Gonadotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D066246:ErbB Receptors; C062876:cetrorelix