In vivo antitumor activity of TT-232 a novel somatostatin analog.
The somatostatin analog TT-232 containing a 5 residue ring, was previously shown to inhibit the proliferation of a large number of cancer cell lines in vitro and reduce the size of tumors in animal models in vivo. Its action is accompanied by inhibition of tyrosine kinases and is characterized by the induction of programmed cell death. On the other hand, it was proved to be free of the endocrine effects of the natural compound. The aim of this study was to find the optimal dose and administration route for in vivo tumor therapy in an animal model. We have investigated the dose--and administration route-dependent antitumor activity of TT-232 on S-180 sarcoma tumor transplanted to inbred BDF1 mice from SPF breeding. Long-term administration (i.p., s.c. and i.v. injections) was started either on the day subsequent to tumor transplantation or after the development of tumor. The antineoplastic potential of TT-232 was evaluated on the basis of survival and tumor growth inhibition. In long-term administration (injections twice a day for 2 weeks) a significant, but dose- and administration route-dependent therapeutic efficacy of TT-232 was observed. The optimum dose of TT-232 15 micrograms/kg which resulted in a 30-40% cure rate and 50-70% growth inhibition in S-180 sarcoma tumor. A moderate antitumor effect was achieved by TT-232 when it was administered after the evelopment of tumor. Our study suggests that TT-232 can be a promising antitumor agent.
Tejeda
M
M
National Institute of Oncology, Department of Experimental Pharmacology, Budapest, Hungary.
Gaal
D
D
Schwab
R E
RE
Pap
A
A
Keri
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D051379:Mice; D009368:Neoplasm Transplantation; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000627:therapeutic use*; D012513:Sarcoma, Experimental / Q000188:drug therapy*; D013004:Somatostatin / Q000031:analogs & derivatives; D016019:Survival Analysis
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C094462:TT2-32; D013004:Somatostatin