Back to Search
Start Over
Down-regulation of protein kinase Cη by antisense oligonucleotides sensitises A549 lung cancer cells to vincristine and paclitaxel
- Source :
- Cancer Letters. 209:177-185
- Publication Year :
- 2004
- Publisher :
- Elsevier BV, 2004.
-
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.
- Subjects :
- Cancer Research
Vincristine
Lung Neoplasms
Paclitaxel
bcl-X Protein
Down-Regulation
Apoptosis
Bcl-xL
Membrane Potentials
chemistry.chemical_compound
Downregulation and upregulation
Tumor Cells, Cultured
medicine
Humans
RNA, Messenger
Protein kinase A
Protein Kinase C
Protein kinase C
biology
Oligonucleotide
Oligonucleotides, Antisense
Antineoplastic Agents, Phytogenic
Mitochondria
Gene Expression Regulation, Neoplastic
Proto-Oncogene Proteins c-bcl-2
Oncology
chemistry
Drug Resistance, Neoplasm
Cancer cell
biology.protein
Cancer research
medicine.drug
Subjects
Details
- ISSN :
- 03043835
- Volume :
- 209
- Database :
- OpenAIRE
- Journal :
- Cancer Letters
- Accession number :
- edsair.doi.dedup.....ee9ebf5565bf6a59bca4c05b4974250d