Hyperbaric oxygen therapy sensitizes nimustine treatment for glioma in mice

Abstract

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.

Nontoxic Targeting of Energy Metabolism in Preclinical VM-M3 Experimental Glioblastoma

“…Therapeutic efficacy in both mice and humans is observed when oxygen partial pressures within the body exceed the partial pressure at normal atmospheric pressure. This enhanced oxygen partial pressure in mice under 2.5 ATM absolute HBO 2 T has been shown experimentally ( 38 , 39 ). With the nontoxic treatments of KD-R, HBO 2 T, and OAA working simultaneously in GBM patients (+/- TMZ), it was predicted that the overall prognosis and survival would significantly increase.…”

Hyperbaric oxygen therapy as adjunctive strategy in treatment of glioblastoma multiforme

“… 45 In a GFP transgenic nude mice model bearing human glioma, the effects of HBO (2.5 ATA for 90 minutes) in sensitizing nimustine chemotherapy were investigated. 46 Following 28 days treatment, HBO inhibited inflammation and glioma cell proliferation as well as reinforcing the effects of nimustine therapy. The underlying mechanism was partially through increasing tumor tissue oxygenation and suppressing the HIF-1α, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), vascular endothelial growth factor (VEGF), matrix metallopeptidase-9 (MMP-9) and nuclear factor-kappa B (NF-κB).…”

“…A few rodent studies support the efficacy of applying HBOT as adjunctive therapy to radio-chemotherapy with underlying mechanism of improved tumor tissue oxygenation and reduced inflammatory response. 44 45 46 However, the application of HBOT alone as therapeutic anti-GBM strategy is not recommended due to the completely opposite findings reported in other studies. The increased tissue hyperoixa by HBOT itself either suppressed 47 48 or promoted 14 49 transplanted glioma tumor growth by its effects on tumor cell apoptosis and tissue angiogenesis.…”

“…The underlying mechanism was partially through increasing tumor tissue oxygenation and suppressing the HIF-1α, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), vascular endothelial growth factor (VEGF), matrix metallopeptidase-9 (MMP-9) and nuclear factor-kappa B (NF-κB). 46 …”

Early Hyperbaric Oxygen Treatment Attenuates Burn-Induced Neuroinflammation by Inhibiting the Galectin-3-Dependent Toll-Like Receptor-4 Pathway in a Rat Model

“…Hyperbaric oxygen (HBO) therapy is a low-cost medical treatment that causes few side effects and utilizes reusable equipment, and it has been commonly applied for many diseases; in this therapy, patient breath 100% oxygen at more than 1.4 atmosphere absolute (ATA) [6]. HBO treatment exerts neuroprotective effects through various mechanisms, including the inhibition of inflammation, reduction of hypoxia, and improvement of microcirculation in the nervous system [7].…”