BIOCHEMICAL AND BIOLOGIC EFFECTS OF SOMATOSTATIN THERAPY ON TUMOR-GROWTH AND HOST METABOLISM

Somatostatin has been shown to have direct antiproliferative activity against various animal and human tumors and may be useful for long-term treatment of cancer patients. However, the metabolic effects of long-term somatostatin therapy have not been studied in the tumor-bearing host. It is known that somatostatin inhibits growth hormone and insulin secretion, and has inhibitory functions at all levels of the gastrointestinal tract. These properties may be especially detrimental to the tumor-bearing host which already suffers the cachectic effect of malignancy. This study examined the effect of the long-term somatostatin analogue octreotide (SMS) on host and tumor tissues in rats bearing a mammary adenocarcinoma (MAC-33). In vitro studies demonstrate that SMS (10-1000 ng/ml) has no direct effect on tumor cell proliferation in this model. Thirty female tumor-bearing Lewis rats were randomized to two groups. The treatment group received 175 mu g/kg SMS injections ip twice daily for 25 days; the placebo group received saline injections by the same route and schedule. Biochemical studies revealed a significant increase in tumor and liver protein/DNA ratio and decreased skeletal muscle protein/DNA content as a result of SMS treatment. These alterations in tumor and muscle composition are indicative of tumor growth and host catabolism. Biologic parameters demonstrated no significant change in carcass weight, tumor weight, or tumor metastasis from SMS treatment. Thus, a discordance is found between gross biologic parameters (indicating no significant effect of SMS) and more subtle biochemical indices (indicating progressive tumor growth and muscle protein catabolism). SMS therapy may produce adverse biochemical effects on host muscle which simulate cachexia when used chronically in the tumor-bearing host.