Inhibition of growth of the transplantable rat chondrosarcoma by analogs of hypothalamic hormones

Abstract

The Swarm chondrosarcoma is a hormone-responsive tumor whose growth is dependent on growth hormone, somatomedins and glucocorticoids. Previous work showed that partial functional hypophysectomy can be achieved by chronic administration of the LHRH analog [D-Trp6]LHRH, which lowers blood levels of LH [luteinizing hormon] and FSH. Somatostatin (SS)-28 or analogs of SS-14 depress serum prolactin, growth hormone and ACTH levels. The effect of s.c. injection of these analogs on the growth of Swarm chondrosarcoma 3 days after transplanting it into male Sprague-Dawley rats was investigated. At autopsy, tumor volume was measured, and tumors and various organs were weighed. In rats treated with 3 different analogs of SS-14, [p-NH2-Phe4]SS, [D-5-F-Trp8]SS and [D-5-MeO-Trp8]SS, in doses of 30 .mu.g once or twice daily for 14-30 days, there was a significant reduction in tumor volume and/or weight as compared with control rats. The longer acting SS-28 or its analog Val-Gly-Tyr-Val-Ile-Leu-Gly-SS-28, given in doses of 30 .mu.g/day for 22-30 days, also significantly decreased tumor weight and/or volume. In 3 experiments, [D-Trp6]LHRH (30-60 .mu.g/day), administered alone or together with analogs of SS-14, decreased tumor weight and/or volume. Serum growth hormone and prolactin levels in rats bearing the tumors were significantly decreased after treatment with [D-5-F-Trp8]SS or with [D-Trp6]LHRH. The inhibition of growth of the Swarm chondrosarcoma in rats by these analogs suggests that they might lead to a new endocrine therapy for chondrosarcomas, osteosarcomas and related hormone-dependent neoplasias.