BREAST-CANCER GROWTH IS INHIBITED BY VASOACTIVE-INTESTINAL-PEPTIDE (VIP) HYBRID, A SYNTHETIC VIP RECEPTOR ANTAGONIST

Breast cancer vasoactive intestinal peptide (VIP) receptors were chara cterized. Using in vitro autoradiographic techniques, I-125-labeled VI P bound with high affinity to breast biopsy sections. I-125-labeled VI P bound specifically to five breast cancer cell lines examined using r eceptor-binding techniques. Specific I-125-labeled VIP binding to MDA- MB-231 cells was inhibited with high affinity by VIP and pituitary ade nylate cyclase-activating polypeptide (IC50 = 2 nM) and with moderate affinity by the VIP hybrid (IC50 = 0.5 mu M). VIP elevated the cAMP in a dose-dependent manner, and VIP hybrid (10 mu M) inhibited the incre ase in cAMP caused by VIP. Using Northern blot analysis, VIP (10 nM) s timulated c-fos and c-myc mRNA, and the increase caused by VIP was rev ersed by the VIP hybrid. The VIP hybrid inhibited breast cancer growth in vitro and 62 vivo using nude mice bearing breast cancer xenografts . These data suggest that the VIP hybrid is a breast cancer VIP recept or antagonist.