Bcl-xL antisense oligonucleotides chemosensitize human glioblastoma cells.

Background: Resistance to chemotherapy in glioblastoma has been linked to the expression of antiapoptotic Bcl-2 family members including Bcl-xL.

Methods: Bcl-xL expression was specifically reduced in M059K glioblastoma cells with antisense oligonucleotides (ISIS 16009, ISIS 16967) as assessed by Western blotting. Induction of apoptosis by treatment with antisense oligonucleotides in combination with paclitaxel in cell culture was monitored by WST-1 assays and flow cytometric analysis.

Results: Antisense oligonucleotide-mediated reduction of Bcl-xL levels led to enhanced cytotoxicity in M059K cells when compared to the use of a mismatch control oligonucleotide (p < 0.001). A decreased threshold for the induction of apoptosis led to significantly enhanced cytotoxic responses to paclitaxel treatment in WST-1 assays (p < 0.001) and flow cytometric analyses.

Conclusion: Combination treatment using Bcl-xL antisense oligonucleotides and paclitaxel may qualify as a promising strategy to ultimately improve the clinical outcome of glioblastoma.