HIF-1α inhibition sensitizes pituitary adenoma cells to temozolomide by regulating MGMT expression

  • Authors:
    • Wenna Chen
    • Zheng Xiao
    • Yachao Zhao
    • Lina Huang
    • Ganqin Du
  • View Affiliations

  • Published online on: August 22, 2013     https://doi.org/10.3892/or.2013.2689
  • Pages: 2495-2501
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Abstract

Suppression of hypoxia-inducible factor 1α (HIF-1α) has been shown to sensitize glioblastoma cells to temozolomide (TMZ) treatment via down-modulation of O6-methylguanine-DNA methyltransferase (MGMT) expression. To date, whether the efficacy of TMZ therapy is correlated with MGMT expression and whether HIF-1α suppression exerts similar effects in human pituitary adenoma cells have not been defined. In the present study, using an HIF-1α knockdown strategy and the HIF-1α inhibitor 2-methoxyestradiol (2ME), we demonstrated for the first time that HIF-1α suppression increases the efficacy of TMZ in human pituitary adenoma cells in vitro and in vivo. Our mechanistic study showed that HIF-1α suppression resulted in down-modulation of MGMT expression and decreased DNA damage repair ability as demonstrated by decreased RAD51 protein expression. These results suggest an HIF-1α-dependent regulation of MGMT expression in human pituitary adenoma cells, and HIF-1α knockdown or the HIF-1α inhibitor 2ME can confer TMZ sensitization in human pituitary adenomas. The clinical application of 2ME as an adjuvant therapy may be a potential approach to improve the efficacy of TMZ therapy for pituitary adenomas.
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November 2013
Volume 30 Issue 5

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

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Copy and paste a formatted citation
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Spandidos Publications style
Chen W, Xiao Z, Zhao Y, Huang L and Du G: HIF-1α inhibition sensitizes pituitary adenoma cells to temozolomide by regulating MGMT expression. Oncol Rep 30: 2495-2501, 2013
APA
Chen, W., Xiao, Z., Zhao, Y., Huang, L., & Du, G. (2013). HIF-1α inhibition sensitizes pituitary adenoma cells to temozolomide by regulating MGMT expression. Oncology Reports, 30, 2495-2501. https://doi.org/10.3892/or.2013.2689
MLA
Chen, W., Xiao, Z., Zhao, Y., Huang, L., Du, G."HIF-1α inhibition sensitizes pituitary adenoma cells to temozolomide by regulating MGMT expression". Oncology Reports 30.5 (2013): 2495-2501.
Chicago
Chen, W., Xiao, Z., Zhao, Y., Huang, L., Du, G."HIF-1α inhibition sensitizes pituitary adenoma cells to temozolomide by regulating MGMT expression". Oncology Reports 30, no. 5 (2013): 2495-2501. https://doi.org/10.3892/or.2013.2689