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

Zhong Wei Xu, Helmut Friess, Marc Solioz, Stefan Aebi, Murray Korc, Jörg Kleeff, Markus W. Büchler

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Pancreatic cancer is one of the leading causes of cancer-related death in Western countries. Bcl-xL 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-xL 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-xL 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-xL 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-xL antisense oligonucleotides enhanced the cytotoxic effects of gemcitabine in pancreatic cancer cells. Our results indicate that Bcl-xL antisense oligonucleotides effectively inhibited pancreatic cancer cell growth and caused apoptosis by reducing Bcl-xL protein levels. Bcl-xL antisense oligonucleotides also increased the chemosensitivity of pancreatic cancer cells, suggesting that Bcl-xL antisense therapy might be a potential future approach in this disease.

Original languageEnglish (US)
Pages (from-to)268-274
Number of pages7
JournalInternational Journal of Cancer
Volume94
Issue number2
DOIs
StatePublished - Oct 15 2001

Keywords

  • Antisense
  • Apoptosis
  • Bcl
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Bcl-x<sub>l</sub> antisense oligonucleotides induce apoptosis and increase sensitivity of pancreatic cancer cells to gemcitabine'. Together they form a unique fingerprint.

  • Cite this