Antitumor activity of the somatostatin structural derivative (TT-232), against mouse and human melanoma tumor models.

BACKGROUND

The somatostatin structural deivative, TT-232, has a special 5'-residue ring structure (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2) and very different characteristics from the known growth hormone (GH) active somatostatin analogs. TT-232 inhibited tyrosine kinase activity of tumor cell lines and this inhibition correlated well with the inhibition of cell proliferation of a large number of cancer cell lines in vitro and reduces the size of different tumors in animal models in vivo. The antitumor efficacy of TT-232 has been found to be associated with the induction of apoptosis in tumor cells, resulting in highly selective elimination of tumor tissue. TT-232 was found to be devoid of GH release inhibitory activity but to possess strong antitumor effects. It binds with a high affinity to SSTR1 and SSTR4. This compound was also found to inhibit inflammation in a number of experimental models.

MATERIALS AND METHODS

The study compared the antitumor effect of TT-232 in various long-term administration routes: an intermittent (injection) versus continuous (infusion) treatment via subcutaneously inserted 2002 type Alzet osmotic minipumps in two different tumor models (B-16 rodent melanoma and HT-18 human lymphoid melanoma). Treatment with TT-232 started after disease development. The antitumor efficacy of TT-232 was evaluated on the basis of tumor growth inhibition and survival time.

RESULTS

In the case of B-16 rodent melanoma, the TT-232 treatments resulted in 35%-39% (injection) and 47%-63% (infusion) tumor growth inhibition, and the infusion treatment an approximately 61% increase in survival time. The tumor growth inhibitory effect of TT-232 on HT-18 lymphoid melanoma tumor proved to be significant, resulting in 41%-63% (injection) and 69%-79% (infusion) decreases in tumor volume and in a 25%-30% increase in survival time (infusion treatments).

CONCLUSION

The results indicate that TT-232 could be a potentially useful therapeutic agent if these data are translated into clinical practice.