Abstract
Glioblastoma (GBM) is a common primary central nervous system tumor. Although the multimodal integrated treatment for GBM has made great progress in recent years, the overall survival time of GBM is still short. Thus, novel treatments for GBM are worth further investigation and exploration. This study aimed to investigate the effects of etomidate on GBM tumor growth and the underlying mechanism. A xenograft tumor model was established and treated with etomidate to assess tumor growth. Immunohistochemistry (IHC) assay evaluated the positive rate of Ki67 cells in tumor tissues. Cell counting kit (CCK)-8 and EdU assays accessed the cell viability and proliferation. Immunofluorescence (IF) staining detected the distribution of macrophage markers in tumor tissues. The percentages of M1- and M2-like macrophages in tumor-associated macrophages (TAMs) and co-culture system (macrophages and GBM cells) were detected using flow cytometry. Macrophage polarization-related genes were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Etomidate treatment inhibited the tumor growth, and increased the CD86+ cells but decreased the CD206+ cells in TAMs. The gene expression of M1 markers was increased in TAMs of etomidate-treated mice, whereas that of M2 markers was decreased. Moreover, etomidate treatment increased the number of CD86+ M1-like macrophages co-cultured with tumor cells but decreased that of CD206+ M2-like macrophages, with the upregulation of M1 markers and downregulation of M2 markers. Etomidate inhibited GBM tumor growth by promoting M1 macrophage polarization, suggesting a new insight into the clinical treatment of GBM.
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Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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All authors participated in the design, interpretation of the studies and analysis of the data and review of the manuscript. C G drafted the work and revised it critically for important intellectual content and was responsible for the acquisition, analysis, and interpretation of data for the work; Y N made substantial contributions to the conception or design of the work and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Animal experiment protocols in this study were approved by the Animal Ethics Committee of The First Affiliated Hospital of Harbin Medical University according to the Guide for the Care and Use of Laboratory Animals (National Research Council).
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Gao, C., Nie, Y. Etomidate inhibits tumor growth of glioblastoma by regulating M1 macrophage polarization. Metab Brain Dis 39, 569–576 (2024). https://doi.org/10.1007/s11011-023-01335-y
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DOI: https://doi.org/10.1007/s11011-023-01335-y