antisense oligonucleotides radiosensitise colon cancer cells

来自 EBSCO

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作者：

V Wacheck，E Selzer，P Günsberg，T Lucas，H Meyer，C Thallinger，BP Monia，B Jansen

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摘要：

Advanced colon cancer is a malignancy with poor response to various treatment modalities including ionising radiation (IR) and chemotherapy. Both IR and chemotherapeutic agents have been shown to act by inducing apoptosis, a type of cell death antagonised by the Bcl-xgene product. Since approximately 60% of human colon cancers express Bcl-x, it was the aim of this study to explore the potential of Bcl-xantisense oligonucleotides as a novel radiosensitisation strategy. Caco-2 colon cancer cells were treated with Bcl-xantisense oligonucleotides in combination with IR or cisplatin, and Bcl-xprotein expression, apoptosis, cell viability and clonogenic survival were examined. Bcl-xantisense oligonucleotide specifically reduced the Bcl-xprotein level by almost 50% in Caco-2 cells. The decreased threshold for the induction of apoptosis resulted in a 300% increase of apoptosis after IR or cisplatin treatment and led to a 60% reduction of cell proliferation beyond response rates achieved with IR. These data suggest that Bcl-xis an important factor contributing to the treatment resistance of human colon cancer. Specific reduction of Bcl-xprotein levels by antisense oligonucleotides qualifies as a promising therapeutic strategy for colon cancer that may help overcome resistance and improve clinical outcome in this malignancy.

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关键词：

antisense oligonucleotides Bcl-x(L) radiosensitisation colon cancer

DOI：

10.1038/sj.bjc.6601254

被引量：

103