Hyperbaric oxygen therapy sensitizes nimustine treatment for glioma in mice

Cancer Med. 2016 Nov;5(11):3147-3155. doi: 10.1002/cam4.851. Epub 2016 Oct 13.


Nimustine (ACNU) has antitumor activities in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are hampered by the hypoxic microenvironment. We examined the combined effects of ACNU and HBO in a GFP transgenic nude mice bearing human glioma model. Mice inoculated with human glioma cells SU3 were randomly divided into the four groups: (A) the control group, (B) the HBOT (HBO therapy) group, (C) the ACNU group, and (D) the HBOT+ACNU group. Tumor size was measured at the indicated time intervals with a caliper; mice were sacrificed 28 days after treatment, and immunohistochemistry staining and western blot analysis were carried out. By the end of the trial, the tumor weights of groups A, B, C, and D were (P < 0.05), 6.03 ± 1.47, 4.13 ± 1.82 (P < 0.05), 2.39 ± 0.25 (P < 0.05), and 1.43 ± 0.38 (P < 0.01), respectively. The expressions of TNF-α, MMP9, HIF-α, VEGF, NF-κB, and IL-1β were associated with the infiltration of inflammatory cells and the inhibition rate of tumor cells. Hyperbaric oxygen therapy (HBOT) could inhibit glioma cell proliferation and inflammatory cell infiltration, and exert a sensitizing effect on ACNU therapy partially through enhancing oxygen pressure (PO2 ) in tumor tissues and lower expression levels of HIF-1α, TNF-α, IL-1β, VEGF, MMP9, and NF-κB.

Keywords: Chemotherapy; glioma stem cell; green fluorescence transgenic nude mice; hyperbaric oxygen therapy; immunity inflammation; transplantation model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biomarkers
  • Body Weight
  • Cell Line, Tumor
  • Disease Models, Animal
  • Glioma / metabolism*
  • Glioma / mortality
  • Glioma / pathology*
  • Glioma / therapy
  • Humans
  • Hyperbaric Oxygenation* / methods
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Inflammation / metabolism
  • Inflammation / pathology
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • NF-kappa B / metabolism
  • Nimustine / pharmacology*
  • Signal Transduction
  • Tumor Burden
  • Tumor Necrosis Factor-alpha / metabolism
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Biomarkers
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Nimustine