Adjuvant hormonal treatment with peptide TY or its analog decreases human pancreatic carcinoma growth

BACKGROUND: Recent studies have revealed decreased pancreatic cancer cell growth upon administration of peptide YY (PYY). We examined whether adjuvant treatment with PYY or its synthetic analog, BIM-43004, would decrease human pancreatic adenocarcinoma growth. MATERIALS AND METHODS: Human pancreatic ductal adenocarcinomas, MiaPaCa-2 and BxPC-3, were cultured and assessed for growth by MTT assay. Pancreatic cancer cells received 500 pmol or PYY or BIM-43004 for 24 hours prior to S-fluorouracil (5-FU; 10 mu g/mL) and leucovorin (40 mu g/mL) administration. Cell membrane epidermal growth factor (EGF) receptors were analyzed by Western blotting after exposure to peptides and chemotherapy. RESULTS: Cancer cell growth was reduced in all groups receiving hormonal pretreatment (23% PYY/S-FU/leucovorin versus control; 27% BIM-43004/5-FU/leucovorin versus control) as compared with groups receiving 5-FU and leucovorin only (16% versus control). The EGF receptor expression was reduced by 30% in cells treated with PYY/5-FU/leucovorin and by 45% in cells treated with BIM/5-FU/leucovorin as compared with control cells without treatment. CONCLUSION: Human pancreatic cancer cell growth is further decreased when pretreated with PYY or its synthetic analog prior to chemotherapy.