The somatostatin analog Sandostatin (SMS201-995) in treatment of DMBA-induced rat mammary tumors

Abstract

The effects of treatment with a somatostatin analog (Sandostatin, SMS201-995) were investigated in female rats with dimethylbenzanthracene (DMBA)-induced rat mammary tumors. A 3-week treatment was performed using sandostatin, the LHRH-agonist buserelin alone, or buserelin in combination with sandostatin. Twice daily sandostatin treatment was performed with dosages of 0.05 microgram, 0.2 microgram, 1 microgram, 5 micrograms, and 20 micrograms. Buserelin was used in a 2 x 5 micrograms/day dosage. The combined results from six different experiments show that the various dosages of sandostatin caused no tumor growth inhibition. Somatostatin receptors could not be demonstrated in these mammary tumors. Sandostatin treatment by daily injections did not suppress levels of growth hormone, prolactin, or epidermal growth factor-like activities. Estrogen (ER) and progesterone (PgR) receptor contents of the mammary tumors were not changed. In contrast, buserelin treatment caused highly significant tumor remission. The combined treatment with sandostatin and buserelin did not alter the treatment results obtained after treatment with buserelin alone. In conclusion, sandostatin treatment in this tumor model had no direct growth inhibitory effect and did not cause an endocrine inhibition of mammary tumor growth. However, these results do not exclude antitumor effects in human breast cancer in view of the presence of somatostatin receptors in approximately 20-45% of human tumors, besides possible different endocrine effects.

Mechanisms of Antineoplastic Action of Somatostatin Analogs

“…This model has been used successfully to predict clinical activity of a number of compounds now used clinically (95). When the DMBA system is used to generate a model of high tumor burden breast cancer, only insignificant activity of octreotide given as single agent is seen (96). On the other hand, when this model is used to generate a model of low tumor burden breast cancer, octreotide has significant antineoplastic activity as a single agent although this is not greater than that of presently available compounds such as tamoxifen (6).…”