Cytotoxic effects of chemokine receptor 4 inhibition by AMD3100 in biliary tract cancer cells: Potential drug synergism with gemcitabine

Mayr,Christian; Neureiter,Daniel; Pichler,Martin; Berr,Frieder; Wagner,Andrej; Kiesslich,Tobias; Namberger,Konrad

doi:10.3892/mmr.2015.3589

Cytotoxic effects of chemokine receptor 4 inhibition by AMD3100 in biliary tract cancer cells: Potential drug synergism with gemcitabine

Authors:
- Christian Mayr
- Daniel Neureiter
- Martin Pichler
- Frieder Berr
- Andrej Wagner
- Tobias Kiesslich
- Konrad Namberger
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Affiliations: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg A‑5020, Austria, Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg A‑5020, Austria, Department of Experimental Therapeutics, UT MD Anderson Cancer Center, Houston, TX 77054, USA, Department of Hematology and Oncology, Klinikum Braunschweig, Braunschweig D‑38118, Germany
Published online on: April 1, 2015 https://doi.org/10.3892/mmr.2015.3589
Pages: 2247-2252

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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.

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