Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions

被引：71
作者：
Lee, Jin Gu [1 ]
Shin, Ju Hye [2 ]
Shim, Hyo Sup [3 ]
Lee, Chang Young [1 ]
Kim, Dae Joon [1 ]
Kim, Young Sam [2 ]
Chung, Kyung Young [1 ]
机构：
[1] Yonsei Univ, Coll Med, Dept Thorac & Cardiovasc Surg, Seoul, South Korea
[2] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea
[3] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea
来源：
RESPIRATORY RESEARCH | 2015年 / 16卷
关键词：
Autophagy; Chemotherapy; Hypoxia; Lung cancer; Resistance; DECREASED EXPRESSION; TUMOR HYPOXIA; SURVIVAL; BECLIN-1; PROLIFERATION; PROTEINS; BNIP3; HIF-1; LC3;
D O I：
10.1186/s12931-015-0285-4
中图分类号：
R56 [呼吸系及胸部疾病];
学科分类号：
摘要：
Background: 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. Methods: In this study, we investigated the role of hypoxia-induced autophagy in acquiring chemo-resistance in both cancer cell (A549) and human cancer tissue Results: 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-naive cancer tissue in Western blot. Conclusion: 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.
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页数：9
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