Hypoxia-induced inhibition of the endocannabinoid system in glioblastoma cells

Sugimoto,Naotoshi; Ishibashi,Hiroaki; Nakamura,Hiroyuki; Yachie,Akihiro; Ohno-Shosaku,Takako

doi:10.3892/or.2017.6048

Hypoxia-induced inhibition of the endocannabinoid system in glioblastoma cells

Authors:
- Naotoshi Sugimoto
- Hiroaki Ishibashi
- Hiroyuki Nakamura
- Akihiro Yachie
- Takako Ohno-Shosaku
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Affiliations: Department of Physiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920‑8640, Japan, Department of Oral and Maxillofacial Surgery, Kanazawa Medical University, Uchinada 920‑0293, Japan, Department of Public Health Pediatrics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920‑8640, Japan, Department of Pediatrics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920‑8640, Japan, Impairment Study, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-0942, Japan
Published online on: October 20, 2017 https://doi.org/10.3892/or.2017.6048
Pages: 3702-3708

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Abstract

The endocannabinoid system plays an important role in the regulation of physiological and pathological conditions, including inflammation and cancer. Hypoxia is a fundamental phenomenon for the establishment and maintenance of the microenvironments in various physiological and pathological conditions. However, the influence of hypoxia on the endocannabinoid system is not fully understood. In the present study, we investigated the effects of hypoxia on the endocannabinoid system in malignant brain tumors. We subjected U-87 MG cells, derived from malignant glioblastoma, to hypoxia (1.5% O2) for 3 days, and evaluated their viability and expression of endocannabinoid-related genes. Hypoxia decreased the expression of cannabinoid receptor 1 and the astrocyte marker glial fibrillary acidic protein, and increased the expression of vascular endothelial growth factor and cyclooxygenase-2, the enzyme responsible for the metabolism of endocannabinoids, in U-87 MG cells. Although cannabinoid receptor (CB) engagement induces cell death in U-87 MG cells in normoxic conditions, CB agonist-induced death was attenuated in hypoxic conditions. These results suggest that hypoxia modifies the endocannabinoid system in glioblastoma cells. Hypoxia-induced inhibition of the endocannabinoid system may aid the development of glioblastoma.

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