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Metformin inhibits the growth of nasopharyngeal carcinoma cells and sensitizes the cells to radiation via inhibition of the DNA damage repair pathway

  • Authors:
    • Haiwen Li
    • Xinggui Chen
    • Ying Yu
    • Zhennan Wang
    • Yufang Zuo
    • Shuhui Li
    • Donghong Yang
    • Shengwen Hu
    • Mei Xiang
    • Zumin Xu
    • Zhonghua Yu

  • View Affiliations

  • Published online on: September 17, 2014     https://doi.org/10.3892/or.2014.3485
  • Pages: 2596-2604
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Abstract

Nasopharyngeal carcinoma (NPC) is a leading cause of cancer-related mortality. Radiotherapy is one of the primary modalities for NPC treatment. However, in patients in the late stages of the disease, the local control rate and overall survival rate remain low. Therefore, it is urgent to identify new targets that can improve the outcome of radiotherapy in this neoplasm. In the present study, we investigated the effects of metformin on the radiosensitivity of NPC cells and explored the potential mechanisms. The radiosensitizing effects of metformin on NPC cells were measured by colony formation assay. Cell apoptosis was assessed by Hoechst 33342 staining analysis. DNA damage was detected by monitoring γ-H2AX foci with immunofluorescence. The changes in apotosis-related and DNA damage repair-related proteins were detected by western blotting. Our study demonstrated that metformin significantly reduced the cell viability, enhanced radiosensitivity and potentiated radiation-induced caspase-9/-3 cleavage in the NPC cells. In addition, metformin plus radiation significantly upregulated the expression of p-ATM, p-ATR, γ-H2AX and downregulated the expression of ATM, ATR, p95/NBS1, Rad50, DNA-PK, Ku70 and Ku80. Therefore, our results suggest that metformin possesses a strong radiosensitizing potential in NPC cells. This radiosensitizing effect was associated with inhibition of DNA double-strand break repair processes through HR repair and the NHEJ repair signaling pathway, thereby enhancing radiation-induced cell apoptosis. These findings imply that metformin is a potent radiation-sensitizing agent and may be a promising candidate for clinical evaluation as part of a combined regimen for the treatment of nasopharyngeal carcinoma.
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December-2014
Volume 32 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • Impact Factor: 3.8
  • Ranked Oncology
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  • CiteScore: 8.5
  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
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Spandidos Publications style
Li H, Chen X, Yu Y, Wang Z, Zuo Y, Li S, Yang D, Hu S, Xiang M, Xu Z, Xu Z, et al: Metformin inhibits the growth of nasopharyngeal carcinoma cells and sensitizes the cells to radiation via inhibition of the DNA damage repair pathway. Oncol Rep 32: 2596-2604, 2014.
APA
Li, H., Chen, X., Yu, Y., Wang, Z., Zuo, Y., Li, S. ... Yu, Z. (2014). Metformin inhibits the growth of nasopharyngeal carcinoma cells and sensitizes the cells to radiation via inhibition of the DNA damage repair pathway. Oncology Reports, 32, 2596-2604. https://doi.org/10.3892/or.2014.3485
MLA
Li, H., Chen, X., Yu, Y., Wang, Z., Zuo, Y., Li, S., Yang, D., Hu, S., Xiang, M., Xu, Z., Yu, Z."Metformin inhibits the growth of nasopharyngeal carcinoma cells and sensitizes the cells to radiation via inhibition of the DNA damage repair pathway". Oncology Reports 32.6 (2014): 2596-2604.
Chicago
Li, H., Chen, X., Yu, Y., Wang, Z., Zuo, Y., Li, S., Yang, D., Hu, S., Xiang, M., Xu, Z., Yu, Z."Metformin inhibits the growth of nasopharyngeal carcinoma cells and sensitizes the cells to radiation via inhibition of the DNA damage repair pathway". Oncology Reports 32, no. 6 (2014): 2596-2604. https://doi.org/10.3892/or.2014.3485