Down-regulation of protein kinase Cη by antisense oligonucleotides sensitises A549 lung cancer cells to vincristine and paclitaxel

Previous studies point to protein kinase C (PKC) isozyme η as a resistance factor in cancer cells. Therefore, we investigated whether down-regulation of PKCη with second generation antisense oligonucleotides (ODNs) would sensitise A549 human lung carcinoma cells to cytostatics. The effects were compared to the outcome of Bcl-xL down-regulation. Upon treatment with antisense ODNs, PKCη and Bcl-xL were both significantly reduced on mRNA and protein level. Down-regulation of either PKCη or Bcl-xL in combination with vincristine or paclitaxel resulted in a significant increase in caspase-3 activity compared to that in the control oligonucleotide treated cells. In addition, PKCη down-regulation augmented vincristine-induced dissipation of mitochondrial transmembrane potential. In conclusion, these results confirm that PKCη might represent a considerable resistance factor and an interesting target to improve anticancer chemotherapy.