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

Abstract:

:Previous studies point to protein kinase C (PKC) isozyme eta as a resistance factor in cancer cells. Therefore, we investigated whether down-regulation of PKCeta 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, PKCeta and Bcl-xL were both significantly reduced on mRNA and protein level. Down-regulation of either PKCeta 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, PKCeta down-regulation augmented vincristine-induced dissipation of mitochondrial transmembrane potential. In conclusion, these results confirm that PKCeta might represent a considerable resistance factor and an interesting target to improve anticancer chemotherapy.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Sonnemann J,Gekeler V,Ahlbrecht K,Brischwein K,Liu C,Bader P,Müller C,Niethammer D,Beck JF

doi

10.1016/j.canlet.2004.02.001

keywords:

subject

Has Abstract

pub_date

2004-06-25 00:00:00

pages

177-85

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304383504001399

journal_volume

209

pub_type

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