INVITRO AND INVIVO ACTIVITY OF ALKYLATING BOMBESIN RECEPTOR ANTAGONISTS ON SMALL-CELL LUNG-CARCINOMA

Bombesin (BN) and bombesin-like peptides are autocrine growth factors for small cell lung carcinoma (SCLC). BN receptor antagonists can ther efore find clinical application in the treatment of this highly malign ant disease. Six peptides belonging to a new class of alkylating BN an alogues have been selected according to their characteristics evidence d on Swiss 3T3 fibroblasts: high binding affinity to BN receptor, rele vant inhibition (>60%) of the proliferative stimulus induced by BN, lo ng-lasting effect and specificity for BN receptor. The six peptides we re able to bind BN receptors on SCLC cells and to inhibit the growth o f two SCLC cell lines: NCI-H69 and NCI-N592. Conversely, they did not inhibit the growth of tumor cell lines devoid of BN receptors. Two of them were tested in vivo on N592 cells transplanted into nude mice. Th e peptide carrying a Cab [p-bis(2chloroethyl) aminobenzoyl] moiety pro ved to be completely inactive. The second peptide, with a Melphalan mo iety (Mel), showed a moderate activity (33-45% of tumor growth inhibit ion) without any toxicity. The low solubility of this compound prevent ed the use of the higher doses in vivo.