Inhibition of growth of human breast carcinomas in vivo by somatostatin analog SMS 201-995: treatment of nude mouse xenografts

Abstract

Minced tumor fragments were xenografted into subcutaneous tissue of the lateral thoracic regions of young adult, virgin female nude mice to study the effects of somatostatin analog SMS 201-995 on growth of estrogen-dependent (MCF-7) and estrogen-independent (BT-20) human breast carcinomas. When tumors became palpable (6 to 10 days), mice were assigned randomly to receive either SMS (4 to 50 micrograms) or acetate buffer (0.2 ml) subcutaneously twice a day. For MCF-7, mean tumor volume was significantly lower on day 20 and days 30 through 50 in SMS-treated mice than in controls (p less than 0.05), and tumor doubling time was increased from 13.2 to 19.0 days. Calculated growth increment was significantly lower with SMS than with buffer treatment (1.1 +/- 0.1 vs 1.9 +/- 0.2) (p less than 0.001). For BT-20, mean tumor volume of SMS-treated mice was slightly, but not significantly, lower than that of controls; however, calculated growth increment was significantly lower for SMS treatment (3.2 +/- 0.3 vs 3.9 +/- 0.4) (p +/- 0.001), and tumor doubling time was increased from 4.0 to 5.8 days. For MCF-7, flow cytometric DNA analysis of tumor biopsy samples demonstrated a reduced G2 + M phase with SMS treatment. We conclude that SMS slows the growth of both MCF-7 and BT-20 human breast cancer xenografts in nude mice and that SMS may be clinically useful in the management of patients with breast carcinoma.