Doramectin inhibits glioblastoma cell survival via regulation of autophagy <em>in vitro</em> and <em>in vivo</em>

Chen,Chen; Liang,Hongsheng; Qin,Ruirui; Li,Xin; Wang,Liwei; Du,Songlin; Chen,Zhihao; Meng,Xiangxi; Lv,Zhonghua; Wang,Qing; Meng,Jing; Gao,Aili

doi:10.3892/ijo.2022.5319

Doramectin inhibits glioblastoma cell survival via regulation of autophagy in vitro and in vivo

Authors:
- Chen Chen
- Hongsheng Liang
- Ruirui Qin
- Xin Li
- Liwei Wang
- Songlin Du
- Zhihao Chen
- Xiangxi Meng
- Zhonghua Lv
- Qing Wang
- Jing Meng
- Aili Gao
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Affiliations: 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, Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
Published online on: February 8, 2022 https://doi.org/10.3892/ijo.2022.5319
Article Number: 29
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 in vitro. 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 in vivo. 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 in vitro and in vivo. The present study suggested that DRM may be an effective drug for the treatment of GBM.

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