Bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II inhibit tumor growth and decrease the levels and mRNA expression of epidermal growth factor receptors in H-69 small cell lung carcinoma

Bombesin antagonists inhibit growth of MDA-MB-435 estrogen-independent breast cancers and decrease the expression of the ErbB-2/HER-2 oncoprotein and c- jun and c- fos oncogenes

“…This result could be due to the fact that RC-3940-II shows a higher binding affinity to GRPRs than RC-3095 (19). Greater responses to RC-3940-II than to RC-3095 have been obtained also in human H-69 SCLCs, OV-1063 ovarian cancers, and MDA-MB-468 and MDA-MB-231 breast cancers (11,13,14,26).…”

“…BN͞GRP antagonists RC-3095 and RC-3940-II, synthesized in our laboratory (9), inhibit growth of various experimental tumors including small cell lung carcinoma (SCLC) and breast cancers xenografted into nude mice (2,8,10,11). Tumor growth inhibition was invariably associated with a significant down-regulation of EGFRs in tumors (11)(12)(13)(14). In previous studies, we evaluated the effects of BN͞GRP antagonists RC-3095 and RC-3940-II on MDA-MB-231 and MDA-MB-468 estrogen-independent human breast cancers (11,14).…”

Mitogenic effects of gastrin-releasing peptide in head and neck squamous cancer cells are mediated by activation of the epidermal growth factor receptor

“…Indirect evidence suggests the potential involvement of EGFR in GRP or BLP signaling. In several in vivo tumor models (including SCLC and estrogen-dependent and estrogen-independent MTX mouse mammary cancers), treatment with a synthetic bombesin/GRP antagonist, RC-3095, resulted in the downregulation of EGFR mRNA expression levels (Pinski et al, 1994;Halmos and Schally, 1997;Szepeshazi et al, 1997;Koppan et al, 1998). Moreover, Liebow et al showed that bombesin and EGF seemed to promote phosphorylation of similar substrates (Liebow et al, 1994).…”

Inhibition of growth of human malignant glioblastoma in nude mice by antagonists of bombesin/gastrin-releasing peptide

“…Peptides of bombesin/GRP family induce cell proliferation by mechanisms that involve stimulation of phosphatidylinositol, Ca 2+ release, and induction of c-fos and c-jun oncogenes (Moody et al, 1987;Spindel et al, 1993;Draoui et al, 1995). Antagonists of bombesin/GRP can inhibit the growth of SCLC in vivo and in vitro (Mahmoud et al, 1991;Pinski et al, 1994a;Koppan et al, 1998;Halmos and Schally, 1997). In addition, antagonistic analog of bombesin/GRP RC-3095 [D-Tpi 6 ,Leu 13 C (CH 2 -NH 2 ),Leu 14 ]bombesin(6 ± 14) developed in our laboratory suppressed the growth of other tumors including gastric, pancreatic, colorectal, breast, prostatic cancers, and brain tumors in vivo (Pinski et al, 1994b, c, d;Szepeshazi et al, 1991Szepeshazi et al, , 1992, supporting the view that bombesin-like peptides are involved in the pathogenesis of a wide range of human tumors.…”