Bcl-xl antisense oligonucleotides induce apoptosis and increase sensitivity of pancreatic cancer cells to gemcitabine

✍ Scribed by Zhong-wei Xu; Helmut Friess; Marc Solioz; Stefan Aebi; Murray Korc; Jörg Kleeff; Markus W. Büchler

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: French
• Weight: 245 KB
• Volume: 94
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.1447

✦ Synopsis

Pancreatic cancer is one of the leading causes of cancerrelated death in Western countries. Bcl-x L is an anti-apoptotic factor of the Bcl-2 family, which is overexpressed in pancreatic cancer and its presence correlates with shorter patient survival. In this study, sequence-specific antisense oligonucleotides targeting the coding region of Bcl-x L were designed to examine whether apoptosis could be induced and chemosensitivity could be increased in pancreatic cancer cells. Five pancreatic cancer cell lines, Panc-1, MIA-PaCa-2, Capan-1, ASPC-1 and T3M4, were treated with Bcl-x L sense or antisense oligonucleotides and gemcitabine and the cell viability was examined by the SRB method. Apoptosis was determined using DAPI staining. In all examined pancreatic cancer cells, Bcl-x L expression was reduced after transfection of the antisense oligonucleotides. Cell death analysis using DAPI staining revealed that antisense, but not sense oligonucleotides caused apoptotic cell death. Furthermore, Bcl-x L antisense oligonucleotides enhanced the cytotoxic effects of gemcitabine in pancreatic cancer cells. Our results indicate that Bcl-x L antisense oligonucleotides effectively inhibited pancreatic cancer cell growth and caused apoptosis by reducing Bcl-x L protein levels. Bcl-x L antisense oligonucleotides also increased the chemosensitivity of pancreatic cancer cells, suggesting that Bcl-x L antisense therapy might be a potential future approach in this disease.