title: Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jin Gu
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hyo Sup
authors.initials: HS
authors.lastname: Shim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Chang Young
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Dae Joon
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Young Sam
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, South Korea. kychu@yuhs.ac.|, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea. kychu@yuhs.ac.
authors.forename: Kyung Young
authors.initials: KY
authors.lastname: Chung
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D000071456:Sequestosome-1 Protein; D013997:Time Factors; D014162:Transfection; D059016:Tumor Microenvironment
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D002945:Cisplatin