1. Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions.
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Jin Gu Lee, Ju Hye Shin, Hyo Sup Shim, Chang Young Lee, Dae Joon Kim, Young Sam Kim, Kyung Young Chung, Lee, Jin Gu, Shin, Ju Hye, Shim, Hyo Sup, Lee, Chang Young, Kim, Dae Joon, Kim, Young Sam, and Chung, Kyung Young
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NON-small-cell lung carcinoma , *CANCER treatment , *AUTOPHAGY , *HYPOXEMIA , *CANCER chemotherapy , *SMALL interfering RNA , *CANCER cells , *ANTINEOPLASTIC agents , *CARRIER proteins , *CELL lines , *CELL physiology , *CISPLATIN , *DRUG resistance in cancer cells , *DOSE-effect relationship in pharmacology , *GENES , *GENETIC techniques , *LUNG cancer , *LUNG tumors , *NERVE tissue proteins , *TIME , *PHARMACODYNAMICS - 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 tissueResults: 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. [ABSTRACT FROM AUTHOR]- Published
- 2015
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