多拉菌素（DRM）是一种阿维菌素药物，已经证实DRM具有抗癌作用。然而，DRM在程序性细胞死亡（PCD）方面的分子机制仍不清楚。本研究旨在确定DRM是否能够诱导胶质瘤细胞的PCD。在此实验中，采用MTT和Ki-67实验检测体外细胞存活率和体内肿瘤增殖。然后，通过转录组比较分析DRM对PCD的影响。接下来，通过透射电子显微镜（TEM）、DNA凝胶电泳、JC-1实验、Western Blotting和qRT-PCR检测内源性凋亡。同时，通过TEM、Hoechst 33342、FITC和PI染色实验、Western Blotting检测坏死样细胞死亡（necroptosis）。我们发现DRM通过Bcl-2/Bax/Caspase-3通路诱导凋亡。此外，DRM还诱导ROS过度产生，然后ROS通过RIPK1/RIPK3/MLKL通路诱导necroptosis，线粒体充当两个通路之间的桥梁。我们的研究提供了DRM抗癌作用的新见解。这些结果表明，DRM可能作为潜在的治疗药物诱导凋亡和necroptosis用于癌症治疗。© 2023年作者，由西班牙肿瘤学会（FESEO）所独家许可。

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).