Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells.
Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells.
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DOI：
10.3892/ijo.26.5.1401
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发表时间：
2005-05
影响因子：
5.2
通讯作者：
Hideaki Ito;S. Daido;T. Kanzawa;S. Kondo;Y. Kondo
中科院分区：
文献类型：
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作者：
Hideaki Ito;S. Daido;T. Kanzawa;S. Kondo;Y. Kondo
自噬是癌细胞对电离辐射（IR）或化疗的一种新反应，但其意义或机制在很大程度上仍不清楚。自噬的特征是细胞质中自噬空泡的显着形成。它是一种涉及自噬/溶酶体区室的蛋白质降解系统。该过程首先隔离一部分细胞质，形成自噬体。然后自噬体与溶酶体融合并裂解其内容物。为了研究特定分子辐射诱导的自噬，我们与饥饿诱导的自噬相比，评估了 IR 后微管相关蛋白轻链 3 (LC3) 表达的变化及其细胞内分布。首先，我们发现在人恶性胶质瘤 U373-MG 细胞中，IR 诱导细胞周期停滞和自噬，但不诱导细胞凋亡。 II 型 LC3 与自噬体膜特异性相关，在 IR 和氨基酸饥饿后增加。外源LC3分布在点状结构上，表明自噬体的形成。自噬抑制剂 3-甲基腺嘌呤和巴弗洛霉素 A1 使 U373-MG 细胞放射增敏。此外，显示 DNA 双链断裂程度的 gammaH2AX 病灶在用 IR 和自噬抑制剂处理的细胞中比仅用 IR 处理的细胞中更明显和更长。我们的结果表明自噬抑制剂可能代表放射增敏治疗恶性胶质瘤细胞的新应用。
Autophagy is a novel response of cancer cells to ionizing radiation (IR) or chemotherapy, but its significance or mechanism remains largely elusive. Autophagy is characterized with the prominent formation of autophagic vacuoles in the cytoplasm. It is a protein degradation system that involves autophagic/lysosomal compartment. The process begins with sequestering a portion of the cytoplasm, forming the autophagosome. The autophagosome then fuses with the lysosome and lyses its contents. To study radiation-induced autophagy with specific molecules, we assessed changes in the expression of microtubule-associated protein light chain 3 (LC3) and its intracellular distribution after IR in comparison with starvation-induced autophagy. First, we showed that IR induced cell cycle arrest and autophagy, but not apoptosis, in human malignant glioma U373-MG cells. Type II LC3, that is specifically associated with the membrane of the autophagosome, increased after IR and amino acid starvation. Exogenous LC3 distributed on punctate structures, indicative of the formation of autophagosomes. Autophagy inhibitors, 3-methyladenine and bafilomycin A1, radiosensitized U373-MG cells. Furthermore, gammaH2AX foci, that show the extent of DNA double-strand breaks, were more pronounced and prolonged in the cells treated with IR and autophagy inhibitors than in those cells treated with IR only. Our results suggest that autophagy inhibitors may represent a new application of radiosensitization for malignant glioma cells.