Effect of doramectin on programmed cell death pathway in glioma cells.

Songlin Du, Hongsheng Liang, Lu Zhou, Chen Chen, Ruimeng Sun, Jie Zhang, Xiangyi Meng, Aili Gao

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 2023 Oct

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Doramectin (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. In 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. We 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. Our 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. © 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).

Citation

Songlin Du, Hongsheng Liang, Lu Zhou, Chen Chen, Ruimeng Sun, Jie Zhang, Xiangyi Meng, Aili Gao. Effect of doramectin on programmed cell death pathway in glioma cells. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2023 Oct;25(10):2871-2883