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

The Swarm chondrosarcoma is a hormone-responsive tumor growth whose growth is dependent on growth hormone, somatomedins, and glucocorticoids. Our previous work showed that that partial functional hypophysectomy can be achieved by chronic administration of the luteinizing hormone-releasing hormone (LH-RH) analog [D-Trp⁶]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-NH₂-Phe⁴]SS, ]D-5-F-Trp⁸]SS, and [D-5-MeO-Trp⁸]SS, in doses of 30 μg 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 μg/day for 22-30 days, also significantly decreased tumor weight and/or volume. In three experiments, [D-Trp⁶]LH-RH (30-60 μg/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]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.