Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Mayr, C; Neureiter, D; Pichler, M; Berr, F; Wagner, A; Kiesslich, T; Namberger, K.
Cytotoxic effects of chemokine receptor 4 inhibition by AMD3100 in biliary tract cancer cells: Potential drug synergism with gemcitabine.
Mol Med Rep. 2015; 12(2):2247-2252
Doi: 10.3892/mmr.2015.3589
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Pichler Martin
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Biliary tract cancer (BTC) remains one of the most life-threatening types of cancer due to the lack of efficient therapies. Advanced tumour stages at the point of diagnosis and high chemoresistance are two of the predominant reasons for a 5-year survival rate of only ~5%. The present study investigated the effect of the chemokine receptor 4 (CXCR4) inhibitor AMD3100 (Plerixafor), alone and in combination with standard gemcitabine chemotherapy, on the proliferation of BTC cells. The expression of CXCR4 was analysed by reverse transcription-quantitative polymerase chain reaction in eight heterogeneously differentiated BTC cell lines. The effects of treatment with the CXCR4 antagonist, AMD3100, on cell viability and anchorage-independent growth, and the possible synergistic cytotoxic effects of AMD3100 with standard chemotherapeutics were assessed. The expression of CXCR4 was observed to a variable extent in all eight BTC cell lines, with SkChA-1 cells exhibiting the highest expression levels. Treatment with AMD3100 led to a marginal decrease in cell viability in the cell lines, with the exception of the CCSW-1 cells, and a significant reduction in the GBC, MzChA-1, SkChA.-1 and TFK-1 cell lines. The combined treatment of the SkChA-1 cells with varying concentrations of AMD3100 and standard gemcitabine chemotherapy revealed a more marked overall cytotoxicity, indicating a potential synergistic effect. In addition, AMD3100 significantly reduced anchorage-independent growth in the SkChA-1 cells. Overall, the results of the present study suggest that the inhibition of CXCR4 by AMD3100, in combination with gemcitabine, may be a suitable strategy for the future therapy of BTC.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Agents - pharmacology
- Apoptosis - drug effects
- Bile Ducts - drug effects
- Bile Ducts - metabolism
- Bile Ducts - pathology
- Cell Line, Tumor -
- Cell Proliferation - drug effects
- Cell Survival - drug effects
- Deoxycytidine - analogs & derivatives
- Deoxycytidine - pharmacology
- Drug Synergism -
- Epithelial Cells - drug effects
- Epithelial Cells - metabolism
- Epithelial Cells - pathology
- Gallbladder - drug effects
- Gallbladder - metabolism
- Gallbladder - pathology
- Gene Expression Regulation, Neoplastic -
- Heterocyclic Compounds - pharmacology
- Humans -
- Receptors, CXCR4 - antagonists & inhibitors
- Receptors, CXCR4 - genetics
- Receptors, CXCR4 - metabolism
- Signal Transduction -
- Find related publications in this database (Keywords)
- biliary tract cancer
- chemokine receptor 4
- AMD3100
- Plerixafor
- viability
- combination treatment
- gemcitabine
- anchorage-independent growth