Department of Bioengineering, College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China.
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Int J Oncol. 2022 Mar;60(3). doi: 10.3892/ijo.2022.5319. Epub 2022 Feb 9.
Glioblastoma (GBM) is one of the most widespread and lethal types of cancer. However, there are currently no drugs or therapeutic strategies that can completely cure GBM. Doramectin (DRM) has a broad range of activities against endoparasites and ectoparasites, and is extensively used in livestock. In the present study, the effect of DRM on the induction of autophagy in U87 and C6 GBM and glioma cell lines, as well as the mechanism of autophagy, were examined. First, transmission electron microscopy, plasmid transfection and western blot analysis demonstrated that DRM could induce autophagy in U87 and C6 cells . Next, MTT and colony formation assays revealed that DRM‑induced autophagy prevented U87 and C6 cell viability and colony formation ratio. In addition, DRM‑induced autophagy promoted U87 and C6 cell apoptosis, as indicated by DAPI analysis and flow cytometry. Furthermore, transcriptome analysis demonstrated that DRM modulated a number of genes and pathways involved in autophagy. In a nude mouse xenograft model, immunohistochemical staining and the TUNEL assay demonstrated that the effect of DRM on the tumor was consistent with that . These data indicated that DRM induced autophagy mainly by blocking the PI3K/AKT/mTOR signaling pathway in GBM cells. DRM‑induced autophagy promoted the inhibition of GBM cell proliferation and apoptosis and . The present study suggested that DRM may be an effective drug for the treatment of GBM.
胶质母细胞瘤(GBM)是最广泛和最致命的癌症类型之一。然而,目前没有药物或治疗策略可以完全治愈 GBM。多拉菌素(DRM)对体内外寄生虫具有广泛的活性,广泛用于牲畜。在本研究中,研究了 DRM 对 U87 和 C6 GBM 和神经胶质瘤细胞系自噬的诱导作用及其自噬机制。首先,透射电子显微镜、质粒转染和 Western blot 分析表明,DRM 可诱导 U87 和 C6 细胞发生自噬。接下来,MTT 和集落形成实验表明,DRM 诱导的自噬可防止 U87 和 C6 细胞的活力和集落形成率。此外,DRM 诱导的自噬促进了 U87 和 C6 细胞的凋亡,这一点通过 DAPI 分析和流式细胞术得到证实。此外,转录组分析表明,DRM 调节了许多与自噬相关的基因和通路。在裸鼠异种移植模型中,免疫组织化学染色和 TUNEL 检测表明,DRM 对肿瘤的作用与体内实验一致。这些数据表明,DRM 主要通过阻断 GBM 细胞中的 PI3K/AKT/mTOR 信号通路诱导自噬。DRM 诱导的自噬促进了 GBM 细胞增殖和凋亡的抑制。本研究表明,DRM 可能是治疗 GBM 的有效药物。