Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells

  • Authors:
    • Xue-Yuan Wu
    • Cui-Pei Hao
    • Ming Ling
    • Chi-Hua Guo
    • Wei Ma
  • View Affiliations

  • Published online on: May 28, 2015     https://doi.org/10.3892/or.2015.4011
  • Pages: 787-794
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Abstract

Adrenomedullin (ADM), a multifunctional regulatory peptide, is potentially induced by hypoxia in physiological and pathological tissues, including many types of malignant tumors. Recent research has demonstrated that ADM expression is highly associated with the prognosis and disease severity of human osteosarcoma. However, the effect of ADM on the apoptosis of osteosarcoma cells and its possible mechanism remain to be elucidated. In the present study, we observed that mRNA and protein levels of ADM were increased in human osteosarcoma SOSP-F5M2 cells under a hypoxic microenvironment induced by cobalt chloride (CoCl2) in a time-dependent manner. Treatment with ADM significantly blunted hypoxic-induced apoptosis, evaluated by Hoechst 33342 staining and Annexin V-FITC/PI labeling. The expression of B-cell lymphoma-2 (Bcl-2) was increased by administration of ADM; meanwhile, this effect was reversed by exogenously adding U0126, a selective inhibitor of MEK or ADM22-52 (ADM-specific receptor antagonist). These results demonstrated that ADM acted as a survival factor to inhibit hypoxic-induced apoptosis via interacting with its receptors CRLR-RAMP (2,3) in osteosarcoma cells. The anti-apoptotic function of ADM was found to be mediated by upregulation of the expression of Bcl-2 partially through activation of the MEK/ERK1/2 signaling pathway. Therefore, targeting of the ADM/ADM acceptors/ERK1/2/Bcl-2 pathway may provide a potential strategy through which to induce the apoptosis of osteosarcoma cells.
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August-2015
Volume 34 Issue 2

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

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Spandidos Publications style
Wu X, Hao C, Ling M, Guo C and Ma W: Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells. Oncol Rep 34: 787-794, 2015.
APA
Wu, X., Hao, C., Ling, M., Guo, C., & Ma, W. (2015). Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells. Oncology Reports, 34, 787-794. https://doi.org/10.3892/or.2015.4011
MLA
Wu, X., Hao, C., Ling, M., Guo, C., Ma, W."Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells". Oncology Reports 34.2 (2015): 787-794.
Chicago
Wu, X., Hao, C., Ling, M., Guo, C., Ma, W."Hypoxia-induced apoptosis is blocked by adrenomedullin via upregulation of Bcl-2 in human osteosarcoma cells". Oncology Reports 34, no. 2 (2015): 787-794. https://doi.org/10.3892/or.2015.4011