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.
Highlights
Hyperbaric oxygen therapy, the noninvasion treatment, has been widely used in many common diseases, such as carbon monoxide poisoning
We found that the hyperbaric oxygen therapy significantly increased the sensitivity of nimustine treatment for mice bearing glioma
It was found that hypoxia of high- grade glioma was severe than that of low-grade glioma, and hypoxia could promote rather than inhibit tumor growth [13,14,15]
Summary
Hyperbaric oxygen therapy, the noninvasion treatment, has been widely used in many common diseases, such as carbon monoxide poisoning. Almost all the hypoxic diseases were adaptive [1], there had been debates over HBO therapy for cancer patients in the past few decades [2, 3]. By using the HBO therapy in mice bearing tumor, Stuhr et al [4] proposed that hyperbaric oxygen might inhibit the growth of glioma cells, subcutaneously transplanted in C57BL/6J mice. HBOT combined with 5-F U and doxorubicin had increased sensitivity in the treatment of solid tumors in mice [5, 6]. The glioma-bearing animals were treated with HBOT, ACNU, or the combination of both. Hyperbaric Oxygen and Nimustine Treating Glioma guaranteed that the nude mice lived in SPF environment, and were not affected by HBOT. We found that the hyperbaric oxygen therapy significantly increased the sensitivity of nimustine treatment for mice bearing glioma
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