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.

ObjectiveDexamethasone (DEX) is a glucocorticoid that is commonly used in clinics. Previously, DEX has been shown to inhibit the function of immune system; however, DEX is often used to treat side reactions, such as nausea and vomiting caused by chemotherapy in clinics. Therefore, it is necessary to study the role of DEX in the treatment of cancer.MethodsThe effects of DEX on HepG2 were studied in vitro by Cell Counting Kit-8 method, cell cycle, and scratch test. The transplanted tumor model of HepG2 was established in nude mice to study the anti-tumor effect of DEX in vivo. In addition, in order to study the effect of DEX on the immune system, we also established a transplanted tumor model of 4T1 in normal immunized mice to study treatment effect and mechanism of DEX in mice of normal immune function.ResultsThe results showed that DEX inhibited the proliferation of HepG2 in vitro and in vivo, affecting the cycle and migration of HepG2 cells, and the expression of c-Myc and the activation of mTOR signaling pathway were inhibited. The expression of key enzymes related to glucose metabolism is altered, especially that of phosphoenolpyruvate carboxykinase2 (PCK2). In normal immunized mice, DEX also inhibits the proliferation of tumor cells 4T1, while the proportion of CD4+CD45+T cells and CD8+CD45+ T cells in CD45+ cells in the lymph nodes upregulated, the proportion of Treg cells in CD4+ T cells downregulated in lymph nodes, and the proportion of MDSCs in tumor tissues downregulated.ConclusionDEX can inhibit tumor cells in vitro and in vivo. The mechanism is to inhibit the activation of mTOR signaling pathway by inhibiting the expression of c-Myc, further affecting the expression of key enzymes involved in glucose metabolism, especially PCK2. In addition, DEX has an inhibitory effect on the immune system, which may be the reason why DEX still has anti-tumor effect in normal mice.

Background: Glioblastoma (GBM) is a highly aggressive cancer having a dismal prognosis. N 6methyladenosine (m 6 A) is closely related to GBM progression. The significance of m 6 A modifications depends on the m 6 A readers, whose functions in glioma progression are largely unknown. This study sought to investigate the expression of the m 6 A related gene in glioma and its effect on the malignant progression of glioma.Methods: The expression differences between low-grade gliomas (LGGs) and high-grade gliomas (HGGs), and among 19 m6A-related genes were analyzed by The Cancer Genome Atlas (TCGA). Survival probability was analyzed in terms of the high or low expression of insulin growth factor-2 binding protein 3 (IGF2BP3) in the TCGA data set. The clinicopathological data of 40 patients with glioma were analyzed retrospectively, and the expression of IGF2BP3 in the tumor tissues was analyzed by immunohistochemistry (IHC). Lentiviral vectors harboring short-hairpin RNA (shRNA) were used to knock down IGF2BP3 in the glioma cell lines U87 and U251, and the results were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. The effects of IGF2BP3 on the proliferation, invasion, and tumorigenicity of the glioma cells were verified by Cell Counting Kit-8 (CCK-8), transwell invasion, and subcutaneous tumorigenesis experiments in nude mice. The cell cycle phases were measured by flow cytometry. Results: The sequencing of TCGA data identified IGF2BP3 as the most significantly altered m 6 A-related gene. Patients with high IGF2BP3 expression had a significantly reduced survival probability (P<0.001) compared to those with low IGF2BP3 expression. IGF2BP3 was more upregulated in the HGGs than the LGGs. The downregulation of IGF2BP3 inhibited the proliferation, migration, and invasiveness of the glioma cells, and xenograft tumor growth in the mice. According to TCGA data, IGF2BP3 was closely related to cell cycle regulators, such as cyclin-dependent kinase 1 (CDK1) and cell-division cycle protein 20 homologue (CDC20). Further, the knockdown of IGF2BP3 affected the expression of CDK1 and the cell cycle process. Conclusions: IGF2BP3 expression in glioma is positively correlated with tumor grade and enhanced glioma cell proliferation, invasion, and tumorigenicity. IGF2BP3 knockdown decreased the expression of CDK1 and the cell cycle process. The current study showed that IGF2BP3 may serve as a biomarker of prognosis and a therapeutic target in glioma.^ ORCID: Xin Zheng, 0000-0003-4133-7614; Chao Sun, 0000-0002-0577-0130.

No abstract

This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.