In vitro and in vivo inhibition of human small cell lung carcinoma (NCI-H69) growth by a somatostatin analogue

An endocrinologically-potent octapeptide analogue of somatostatin (SRIF), 3-(2-naphthyl)-D-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (BIM-23014 C), was examined for its ability to inhibit the in vitro and in vivo growth of the human small cell lung carcinoma (SCLC) line, NCI-H69. When cultured cells were implanted into athymic nude mice, treatment (500 micrograms/injection, twice daily) resulted in a prolongation of lag time for the appearance of measurable tumors, and there was a marked inhibition of the growth rate. Indeed, peptide injection in the region of the tumor resulted in a complete regression of the NCI-H69 tumors. Withdrawal of BIM-23014 C treatment resulted in an acceleration of tumor growth indicating an antiproliferative rather the oncolytic action. A similar inhibition of tumor growth was also observed when solid tumors obtained from the first implantation were used as the donor tissues. In cell culture, the proliferation in the presence of a low concentration (10nM) of BIM-23104 C was also significantly retarded suggesting a direct mechanism of action.