Open Access

Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway

  • Authors:
    • Zi-Qian Zhang
    • Xue Wang
    • Bing-Hua Xue
    • Yun Zhao
    • Fang Xie
    • Shi-Da Wang
    • Cong Xue
    • Ying Wang
    • Yan-Shu Zhang
    • Ling-Jia Qian
  • View Affiliations

  • Published online on: July 23, 2021     https://doi.org/10.3892/or.2021.8153
  • Article Number: 202
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

High malignancy and high mortality of glioma render it urgent to elucidate the underlying mechanisms of glioma carcinogenesis and explore novel targets for therapy. Epidemiologic and clinical studies have revealed that chronic stress promotes the progression of various solid tumors and is correlated with poor prognosis; however, findings reporting the involvement of chronic stress in glioma are rare. In the present study, a chronic restraint animal model and a chronic stress cell model were established to explore the effects of chronic stress on glioma and its molecular mechanisms. The results revealed that chronic stress promoted glioma growth in vivo, and the serum levels of the stress hormones glucocorticoid (GC) and noradrenaline (NE) were significantly increased. In addition, GC and NE were verified to accelerate the proliferation of glioma cells in vitro. Mechanistically, the phosphatidylinositol 3‑kinase (PI3K)/Akt signaling pathway was revealed to be activated under stress conditions, and inhibition of the expression of p‑Akt could restrain the stress hormone‑induced glioma cell proliferation. In addition, our data indicated that the GC receptor (GR) and β‑adrenergic receptors (ADRBs) were both required for the biological functions of GC and NE in glioma cells. In conclusion, these results indicated that chronic stress and the stress hormones GC and NE activated PI3K/Akt signaling through binding to GR and ADRBs, thereby promoting glioma cell growth. Our findings may provide potential therapeutic targets and pave the way for the development of new strategies to protect patients with glioma from the detrimental effects of stress on tumor progression.
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September-2021
Volume 46 Issue 3

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
Zhang Z, Wang X, Xue B, Zhao Y, Xie F, Wang S, Xue C, Wang Y, Zhang Y, Qian L, Qian L, et al: Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway. Oncol Rep 46: 202, 2021
APA
Zhang, Z., Wang, X., Xue, B., Zhao, Y., Xie, F., Wang, S. ... Qian, L. (2021). Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway. Oncology Reports, 46, 202. https://doi.org/10.3892/or.2021.8153
MLA
Zhang, Z., Wang, X., Xue, B., Zhao, Y., Xie, F., Wang, S., Xue, C., Wang, Y., Zhang, Y., Qian, L."Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway". Oncology Reports 46.3 (2021): 202.
Chicago
Zhang, Z., Wang, X., Xue, B., Zhao, Y., Xie, F., Wang, S., Xue, C., Wang, Y., Zhang, Y., Qian, L."Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway". Oncology Reports 46, no. 3 (2021): 202. https://doi.org/10.3892/or.2021.8153