Abstracts
1997 Digestive Disease Week

Peptide YY and apoptosis: clues to chemotherapy resistance in colon cancer.

K Kling, A Rongione, B Mai, K Kwan, D McFadden. UCLA Department of Surgery, Los Angeles, CA.

OBJECTIVE: Certain gastrointestinal peptides, including somatostatin and peptide YY, (PYY) have demonstrable antineoplastic properties. We have shown that PYY inhibits pancreatic, colon, and breast cancer growth. Many gastrointestinal malignancies are associated with increased levels of a protein (bcl-2) that inhibits both programmed cell death (apoptosis) and chemotherapy-induced cell death. In this study, we test the hypothesis that peptide chemotherapy is mechanistically associated with the regulation of apoptosis and that molecular inhibition of apoptosis renders colon cancer cells resistant to treatment with these peptides. METHODS: Colon adenocarcinoma Caco2 cells were seeded at 5000 cells/well in 96-well plates. After 12 hours, wells were treated with 50µl of media or media containing 1.25µM PYY. Plates were incubated for 36 hours before MTT tetrazolium bromide assay was performed to evaluate mitochondrial activity and viability. Protein was harvested from Caco2 cells treated with 1.25µM PYY and immunoblot analysis of the bcl-2 gene product was performed using bcl-2 polyclonal antibody. RESULTS: PYY treatment resulted in a 28% decrease in cell viability (p<0.00001). Densitometric measurement of the immunoblots demonstrated a 33% increase in bcl-2 expression in surviving cells (p<0.05). CONCLUSIONS: We have found that colon cancer cells resistant to PYY treatment express higher levels of bcl-2 protein, suggesting that the presence of this protein may protect the colon cancer cell from PYY-induced apoptosis. Suppression of proteins that inhibit apoptosis is a potential strategy to improve chemotherapy efficacy. Additionally, the quantification of cellular bcl-2 levels may have predictive value for chemotherapy response.