Inhibition of growth of the transplantable rat chondrosarcoma by analogs of hypothalamic hormones.
The Swarm chondrosarcoma is a hormone-responsive tumor whose growth is dependent on growth hormone, somatomedins, and glucocorticoids. Our previous work showed that partial functional hypophysectomy can be achieved by chronic administration of the luteinizing hormone-releasing hormone (LH-RH) analog [D-Trp(6)]LH-RH, which lowers blood levels of LH and follicle-stimulating hormone. We have also demonstrated that somatostatin (SS)-28 or analogs of SS-14 depress serum prolactin, growth hormone, and corticotropin (ACTH) levels. Consequently, we investigated the effect of subcutaneous injection of these analogs on the growth of Swarm chondrosarcoma 3 days after transplanting it into male Sprague-Dawley rats. At autopsy, tumor volume was measured and tumors and various organs were weighed. In rats treated with three different analogs of SS-14, [p-NH(2)-Phe(4)]SS, [D-5-F-Trp(8)]SS, and [D-5-MeO-Trp(8)]SS, in doses of 30 mug 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 mug/day for 22-30 days, also significantly decreased tumor weight and/or volume. In three experiments, [D-Trp(6)]LH-RH (30-60 mug/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-Trp(8)]SS or with [D-Trp(6)]LH-RH. 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.
D000818:Animals; D002813:Chondrosarcoma / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use*; D013006:Growth Hormone / Q000097:blood; D006728:Hormones / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011388:Prolactin / Q000097:blood; D051381:Rats; D013004:Somatostatin / Q000627:therapeutic use*
D006728:Hormones; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; D011388:Prolactin; D013006:Growth Hormone