Effect of doramectin on programmed cell death pathway in glioma cells

被引：5
作者：
Du, Songlin [1 ]
Liang, Hongsheng [2 ]
Zhou, Lu [1 ]
Chen, Chen [1 ]
Sun, Ruimeng [1 ]
Zhang, Jie [2 ]
Meng, Xiangyi [2 ]
Gao, Aili [1 ]
机构：
[1] Northeast Agr Univ, Coll Life Sci, Dept Biochem & Mol Biol, Harbin 150030, Peoples R China
[2] Harbin Med Univ, Dept Neurosurg, Affiliated Hosp 1, Harbin 150001, Peoples R China
来源：
CLINICAL & TRANSLATIONAL ONCOLOGY | 2023年 / 25卷 / 10期
基金：
中国国家自然科学基金;
关键词：
Doramectin; Programmed cell death; Apoptosis; Necroptosis; ROS; IN-VITRO; NECROPTOSIS; THERAPY;
D O I：
10.1007/s12094-023-03147-z
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
PurposeDoramectin (DRM) is a kind of avermectin drugs, and it has been shown that DRM has anti-cancer effects. However, the molecular mechanism of DRM in programmed cell death (PCD) aspects is still unclear. The objective of this study was to confirm whether DRM induced PCD in glioma cells.MethodsIn this experiment, the MTT assay and Ki-67 assay were used to detect in vitro cell viability and in vivo tumor proliferation. Then, the effect of DRM on PCD was analyzed by transcriptome comparison. Next, Endogenous apoptosis was detected by transmission electron microscopy (TEM), the DNA gel electrophoresis, JC-1 assay, western blotting and qRT-PCR. Meanwhile, necroptosis was detected by TEM, Hoechst 33342, FITC and PI staining assay, western blotting.ResultsWe found DRM induced apoptosis through Bcl-2/Bax/Caspase-3 pathway. And, DRM induced ROS overproduction, then ROS caused necroptosis through RIPK1/RIPK3/MLKL pathway, Mitochondria acted as a bridge between the two pathways.ConclusionOur research provided new insight with the function of anti-cancer of DRM. These results demonstrated DRM may be used as potential therapeutic agents inducing apoptosis and necroptosis for cancer therapy.
引用
收藏
页码：2871 / 2883
页数：13
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