A
somatostatin structural derivative (TT-232) has been developed in our laboratory with strong antiproliferative effect but no GH- release inhibitory activity.
TT-232 inhibited
tyrosine kinase activity of
tumor cells lines and this inhibition correlated well with the inhibition of cell proliferation. The
antineoplastic activity of
TT-232 has been found to be associated with induction of programmed cell death (apoptosis) in
tumor cell, resulting in highly selective elimination of neoplastic tissue. The aim of this study was the therapeutic efficacy of
TT-232 on different human models: PC-3 prostate
carcinoma, MDA-MB-231 (ER-) and MCF-7 (ER+)
breast carcinoma, HT-29 colon
carcinoma, HT-18
melanoma, HL-60 promyelocytic
leukemia. We studied the therapeutic efficacy of the novel
somatostatin analog, it for 30 days with intermittent injection once daily and for 14 days with s.c. infusion using the Alzet osmotic minipump (model 2002). The antitumor activity of
TT-232 was evaluated on the basis of survival time and
tumor growth inhibition. The
tumor growth inhibitory effect of
TT-232 on human
tumor xenografts proved to be significant, resulting in 30%-80% decrease in
tumor volume and in 20-60%
tumor free animals. This antitumor efficacy of the novel
somatostatin analog was observable in almost all
tumors investigated. These data suggest that the novel
somatostatin analog (TT-232) is an effective and promising
antitumor agent.