Grwoth Inhibition of Mouse MXT Mammary Tumor by the Luteinizing Hormone-Releasing Hormone Antagonist SB-75

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Abstract
Female BDF 1 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-Cit 6 , D-Ala 10 ]-LH-RH (SB-75), with the agonist D-Trp 6 -LH-RH, with tamoxifen (5 μg per animal per day subcutaneously), with the combination of D-Trp 6 -LH-RH and tamoxifen, or by surgical ovariectomy. SB-75 and D-Trp 6 -LH-RH were administered in the form of microscapsules releasing 25 μg/day. The reduction in tumor weights after treatment with SB-75, D-Trp 6 -LH-RH, D-Trp 6 -LH-RH plus tamoxifen, or overiectomy 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. [J Natl Cancer Inst 82:513–517, 1990]