Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Skoda, C; Erovic, BM; Wachek, V; Vormittag, L; Wrba, F; Martinek, H; Heiduschka, G; Kloimstein, P; Selzer, E; Thurnher, D.
Down-regulation of Mcl-1 with antisense technology alters the effect of various cytotoxic agents used in treatment of squamous cell carcinoma of the head and neck.
Oncol Rep. 2008; 19(6):1499-1503
Web of Science
PubMed
- Leading authors Med Uni Graz
- Thurnher Dietmar
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- Abstract:
- Antisense oligonucleotides have recently been identified as new anticancer agents. Since human head and neck cancer cells highly express the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1), the aim of this study was to explore the efficacy of the Mcl-1 suppression in combination with various cytotoxic agents in the head and neck cancer cell line SCC9. After oligonucleotide transfection and/or treatment with cisplatin, 5-fluorouracil (5-FU), gemcitabine, paclitaxel or cetuximab, proliferation assays were performed to determine cell viability. The expression patterns of Mcl-1, Bax and Bak were assessed by Western blot analysis and the apoptotic cells were determined by immunohistochemistry using the M30 antibody. A combined Mcl-1 antisense oligonucleotide treatment with paclitaxel, cetuximab and gemcitabine led to a significant reduction in the viable cells. However, the combination with cisplatin and 5-FU showed only moderate synergistic cytotoxic effects. According to the cytotoxic data, distinct apoptosis rates were observed after the combined treatment with the different substances. Western blot analysis also showed a significant suppression of the Mcl-1 synthesis. Our data show that the Mcl-1 antisense oligonucleotide in combination with certain cytotoxic agents has the potential to significantly decrease cell viability in vitro.
- Find related publications in this database (using NLM MeSH Indexing)
- Antibodies, Monoclonal - administration & dosage
- Antibodies, Monoclonal, Humanized -
- Antineoplastic Combined Chemotherapy Protocols - therapeutic use
- Apoptosis - drug effects
- Apoptosis - physiology
- Blotting, Western -
- Carcinoma, Squamous Cell - drug therapy
- Carcinoma, Squamous Cell - genetics
- Carcinoma, Squamous Cell - metabolism
- Cell Survival - drug effects
- Cell Survival - physiology
- Cetuximab -
- Cisplatin - administration & dosage
- Combined Modality Therapy -
- Deoxycytidine - administration & dosage
- Deoxycytidine - analogs & derivatives
- Down-Regulation -
- Fluorouracil - administration & dosage
- Head and Neck Neoplasms - drug therapy
- Head and Neck Neoplasms - genetics
- Head and Neck Neoplasms - metabolism
- Humans -
- Immunoenzyme Techniques -
- Myeloid Cell Leukemia Sequence 1 Protein -
- Oligonucleotides, Antisense - pharmacology
- Paclitaxel - administration & dosage
- Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors
- Proto-Oncogene Proteins c-bcl-2 - genetics
- Proto-Oncogene Proteins c-bcl-2 - metabolism
- Tumor Cells, Cultured -
- bcl-2 Homologous Antagonist-Killer Protein - metabolism
- bcl-2-Associated X Protein - metabolism
- Find related publications in this database (Keywords)
- myeloid cell leukemia-1
- antisense
- apoptosis
- head and neck squamous cell carcinoma
- cancer