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首页> 外文期刊>Journal of International Medical Research >The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: An in?vitro and in?vivo study
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The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: An in?vitro and in?vivo study

机译:蛋白酶体抑制剂lacyacystin通过凋亡发挥其对神经胶质瘤的治疗作用:体内和体外研究

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Objective To examine the effect and underlying mechanism of action of the proteasome inhibitor lactacystin on glioma, in?vitro and in?vivo. Methods Rat C6 glioma cells were cultured with or without lactacystin. Cell proliferation, apoptosis and mitochondrial membrane potential were determined. A glioma xenograft model was established in mice and animals were treated with 0, 1 or 5?μg/20?g body weight lactacystin for 7 days. Animals were sacrificed on day 17 after completion of treatment. Apoptosis in tumour tissue was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Levels of B cell lymphoma 2 (Bcl-2), and Bcl2-associated X protein (Bax) protein and mRNA, were determined in C6 cells and tumour tissues. Results Lactacystin significantly inhibited the proliferation of C6 cells, increased apoptosis and reduced mitochondrial membrane potential in?vitro, and suppressed tumour growth in?vivo. Lactacystin increased the ratio of Bax to Bcl-2 at the mRNA and protein levels, both in?vitro and in?vivo. Conclusions The effects of lactacystin are associated with apoptosis induction. Proteasome inhibition may represent an effective treatment option for glioma.
机译:目的探讨蛋白酶体抑制剂乳胞素对体外和体内神经胶质瘤的作用及其作用机理。方法在有或没有乳腺素的情况下培养大鼠C6神经胶质瘤细胞。测定细胞增殖,凋亡和线粒体膜电位。在小鼠中建立神经胶质瘤异种移植模型,并以0、1或5μg/20μg体重的乳腺激素治疗动物7天。治疗完成后第17天处死动物。通过末端脱氧核苷酸转移酶dUTP缺口末端标记染色检查肿瘤组织中的细胞凋亡。测定了C6细胞和肿瘤组织中B细胞淋巴瘤2(Bcl-2)以及与Bcl2相关的X蛋白(Bax)蛋白和mRNA的水平。结果乳杆菌肽在体外显着抑制C6细胞的增殖,增加凋亡并降低线粒体膜电位,并抑制体内肿瘤的生长。乳酸菌素在体外和体内均增加了mRNA和蛋白质水平上Bax与Bcl-2的比率。结论乳胞素的作用与细胞凋亡的诱导有关。蛋白酶体抑制可能代表神经胶质瘤的有效治疗选择。

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