Moxidectin inhibits glioma cell viability by inducing G0/G1 cell cycle arrest and apoptosis

Song,Dandan; Liang,Hongsheng; Qu,Bo; Li,Yijing; Liu,Jingjing; Chen,Chen; Zhang,Daming; Zhang,Xiangtong; Gao,Aili

doi:10.3892/or.2018.6561

Moxidectin inhibits glioma cell viability by inducing G0/G1 cell cycle arrest and apoptosis

Authors:
- Dandan Song
- Hongsheng Liang
- Bo Qu
- Yijing Li
- Jingjing Liu
- Chen Chen
- Daming Zhang
- Xiangtong Zhang
- Aili Gao
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Affiliations: School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China, Key Laboratory of Neurosurgery, College of Heilongjiang Province; The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China, Key Laboratory of Neurosurgery, College of Heilongjiang Province; The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: July 12, 2018 https://doi.org/10.3892/or.2018.6561
Pages: 1348-1358
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Moxidectin (MOX), a broad‑spectrum antiparasitic agent, belongs to the milbemycin family and is similar to avermectins in terms of its chemical structure. Previous research has revealed that milbemycins, including MOX, may potentially function as effective multidrug resistance agents. In the present study, the impact of MOX on the viability of glioma cells was examined by MTT and colony formation assay, and the molecular mechanisms underlying MOX‑mediated glioma cell apoptosis were explored by using flow cytometry and apoptosis rates. The results demonstrated that MOX exerts an inhibitory effect on glioma cell viability and colony formations in vitro and xenograft growth in vivo and is not active against normal cells. Additionally, as shown by western blot assay, it was demonstrated that MOX arrests the cell cycle at the G0/G1 phase by downregulating the expression levels of cyclin‑dependent kinase (CDK)2, CDK4, CDK6, cyclin D1 and cyclin E. Furthermore, it was revealed that MOX is able to induce cell apoptosis by increasing the Bcl‑2‑associated X protein/B‑cell lymphoma 2 ratio and activating the caspase‑3/‑9 cascade. In conclusion, these results suggest that MOX may inhibit the viability of glioma cells by inducing cell apoptosis and cell cycle arrest, and may be able to function as a potent and promising agent in the treatment of glioma.

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