Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions.
Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions.
复制标题
自噬在低氧条件下有助于非小细胞肺癌的化学抗性。
DOI：
10.1186/s12931-015-0285-4
复制
发表时间：
2015-11-09
影响因子：
5.8
通讯作者：
Chung KY
中科院分区：
文献类型：
--
作者：
Lee JG;Shin JH;Shim HS;Lee CY;Kim DJ;Kim YS;Chung KY
非小细胞肺癌化疗耐药的发展是治疗的主要障碍。缺氧是实体瘤常见的微环境，与肿瘤细胞自噬和化疗耐药有关。在这项研究中，我们研究了低氧诱导的自噬在癌细胞（A549）和人癌组织中获得化学抗性中的作用。A549细胞的低氧暴露（1%O2）刺激癌细胞中的自噬诱导，表现为Western印迹中LC 3BI向LC 3BII转化的增加和p62/螯合体1的减少，共聚焦显微镜中GFP-LC斑点的增加，电镜下双膜自噬泡增多。低剂量暴露还诱导癌细胞对顺铂的抗性，并且LC 3B siRNA恢复癌细胞对化疗的敏感性。此外，与未经化疗的癌组织相比，经历化疗的人肺癌组织在Western印迹中显示LC 3BI向LC 3BII的转化增加和p62/隔离体1的减少。自噬可能在肺癌化疗耐药中起重要作用，缺氧相关通路可能参与了自噬的诱导。
The development of chemo-resistance in non-small lung cancer is a major obstacle in treating patients. Hypoxia is a commonly faced microenvironment in solid tumor and suggested to be related to both autophagy and chemo-resistance. In this study, we investigated the role of hypoxia-induced autophagy in acquiring chemo-resistance in both cancer cell (A549) and human cancer tissue Hypoxic exposure (1 % O2) of A549 cell stimulated autophagic induction in cancer cells, shown by increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 in Western blot, increased GFP-LC puncta in confocal microscopy, and increased number of double-membrane autophagic vacuoles in electron micrographs. Hypoxic exposure also induced resistance of cancer cells to cisplatin, and LC3B siRNA restored the sensitivity of cancer cells to chemotherapy. Furthermore, Human lung cancer tissues that experienced chemotherapy showed increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 compared with chemo-naïve cancer tissue in Western blot. Autophagy may play an important role in acquiring resistance to chemotherapy in lung cancer and hypoxia related pathway seems to be involved in autophagy induction.