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July-2016 Volume 14 Issue 1

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Article

Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A

  • Authors:
    • Jiaxin Fu
    • Han Jiang
    • Chenxuan Wu
    • Yi Jiang
    • Lianping Xiao
    • Yonggang Tian
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, Tianjin Third Central Hospital, Tianjin 300170, P.R. China
  • Pages: 995-1001
    |
    Published online on: May 17, 2016
       https://doi.org/10.3892/mmr.2016.5290
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Abstract

Ewing's sarcoma, the second most common type of malignant bone tumor, generally occurs in children and young adults. The current treatment of Ewing's sarcoma comprises systemic anti‑cancer chemotherapy with complete surgical resection. However, the majority of patients with Ewing's sarcoma develop resistance to chemotherapy. The present study revealed an oncogenic role of lactate dehydrogenase‑A (LDHA) in the resistance of Ewing's sarcoma to cetuximab. LDHA was shown to be upregulated at the protein and mRNA level in cetuximab‑resistant Ewing's sarcoma tissues and a cell line. In addition, a link between LDHA‑induced glycolysis and cetuximab resistance in Ewing's sarcoma cells was revealed. Of note, inhibition of LDHA by either small interfering RNA or LDHA inhibitor oxamate significantly re‑sensitized cetuximab‑resistant cells to cetuximab. Combined treatment with LDHA inhibitor and cetuximab synergistically reduced the viability of cetuximab-resistant cells through the suppression of LDHA. The present study revealed a novel mechanism of cetuximab resistance from the perspective of cancer‑cell metabolism and provided a sensitization approach, which may aid in the development of anti-chemoresistance strategies for the treatment of cetuximab-resistant Ewing's sarcoma.
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Copy and paste a formatted citation
Spandidos Publications style
Fu J, Jiang H, Wu C, Jiang Y, Xiao L and Tian Y: Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A. Mol Med Rep 14: 995-1001, 2016.
APA
Fu, J., Jiang, H., Wu, C., Jiang, Y., Xiao, L., & Tian, Y. (2016). Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A. Molecular Medicine Reports, 14, 995-1001. https://doi.org/10.3892/mmr.2016.5290
MLA
Fu, J., Jiang, H., Wu, C., Jiang, Y., Xiao, L., Tian, Y."Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A". Molecular Medicine Reports 14.1 (2016): 995-1001.
Chicago
Fu, J., Jiang, H., Wu, C., Jiang, Y., Xiao, L., Tian, Y."Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A". Molecular Medicine Reports 14, no. 1 (2016): 995-1001. https://doi.org/10.3892/mmr.2016.5290
Copy and paste a formatted citation
x
Spandidos Publications style
Fu J, Jiang H, Wu C, Jiang Y, Xiao L and Tian Y: Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A. Mol Med Rep 14: 995-1001, 2016.
APA
Fu, J., Jiang, H., Wu, C., Jiang, Y., Xiao, L., & Tian, Y. (2016). Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A. Molecular Medicine Reports, 14, 995-1001. https://doi.org/10.3892/mmr.2016.5290
MLA
Fu, J., Jiang, H., Wu, C., Jiang, Y., Xiao, L., Tian, Y."Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A". Molecular Medicine Reports 14.1 (2016): 995-1001.
Chicago
Fu, J., Jiang, H., Wu, C., Jiang, Y., Xiao, L., Tian, Y."Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A". Molecular Medicine Reports 14, no. 1 (2016): 995-1001. https://doi.org/10.3892/mmr.2016.5290
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