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

 Jin Gu Lee  ;  Ju Hye Shin  ;  Hyo Sup Shim  ;  Chang Young Lee  ;  Dae Joon Kim  ;  Young Sam Kim  ;  Kyung Young Chung 
 RESPIRATORY RESEARCH, Vol.9(16) : 138, 2015 
Journal Title
Issue Date
Adaptor Proteins, Signal Transducing/metabolism ; Antineoplastic Agents/pharmacology* ; Autophagy/drug effects* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/ultrastructure ; Cell Hypoxia ; Cell Line, Tumor ; Cisplatin/pharmacology* ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm* ; Humans ; Lung Neoplasms/drug therapy* ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/ultrastructure ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; RNA Interference ; Sequestosome-1 Protein ; Time Factors ; Transfection ; Tumor Microenvironment*
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-naïve 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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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Dae Joon(김대준)
Kim, Young Sam(김영삼) ORCID logo https://orcid.org/0000-0001-9656-8482
Shin, Ju Hye(신주혜)
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Lee, Jin Gu(이진구)
Lee, Chang Young(이창영)
Chung, Kyung Young(정경영)
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