The antitumour effect of the somatostatin analogue TT-232 depends on the treatment regimen

Abstract

The somatostatin analogue TT-232, containing a five residue ring structure, has a strong antitumour activity both in vitro and in vivo. This peptide has no effect on growth hormone (GH) release, but exhibits a remarkable tyrosine kinase inhibitory effect and induced apoptosis. We studied the effect of TT-232 in different routes of administration and treatment schedules on various types of mouse tumour models. The infusion treatment with inserted Alzet osmotic minipumps proved to be superior to both twice daily subcutaneous (s.c.) or intravenous (i.v.) injections in a 2 weeks period. In the case of S-180 tumour the infusion treatment resulted in 77–100% tumour growth inhibition and in 40–60% of mice long-term and tumour-free survivors. With the P-388sc tumour the infusion of TT-232 resulted in 20–40% of animals long-term and tumour-free survivors and in 76–100% tumour growth inhibition. In the very aggressive Colon-26 (C-26) and MXT, the TT-232 treatment resulted in 71–75% tumour growth inhibition and increased survival time by about 50%.