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Hypoxia-induced autophagy mediates cisplatin resistance in lung cancer cells
by
Wu, Hui-Mei
, Ding, Pei-Shan
, Jiang, Zi-Feng
, Shao, Li-Jie
, Liu, Rong-Yu
in
13/1
/ 13/109
/ 13/2
/ 13/31
/ 13/51
/ 13/89
/ 13/95
/ 14/19
/ 14/34
/ 631/67/1059/2326
/ 631/67/327
/ 82/1
/ Antineoplastic Agents - administration & dosage
/ Apoptosis
/ Autophagy
/ Autophagy - drug effects
/ BNIP3 protein
/ Cell death
/ Cell Hypoxia - drug effects
/ Cell Line, Tumor
/ Chemoresistance
/ Cisplatin
/ Cisplatin - administration & dosage
/ Dose-Response Relationship, Drug
/ Drug Resistance, Neoplasm - drug effects
/ Humanities and Social Sciences
/ Humans
/ Hypoxia
/ Lung cancer
/ Lung Neoplasms - drug therapy
/ Lung Neoplasms - metabolism
/ Lung Neoplasms - pathology
/ Mortality
/ multidisciplinary
/ Neoplasm Proteins - metabolism
/ Oxygen - metabolism
/ Phagocytosis
/ Science
/ siRNA
/ Solid tumors
2015
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Hypoxia-induced autophagy mediates cisplatin resistance in lung cancer cells
by
Wu, Hui-Mei
, Ding, Pei-Shan
, Jiang, Zi-Feng
, Shao, Li-Jie
, Liu, Rong-Yu
in
13/1
/ 13/109
/ 13/2
/ 13/31
/ 13/51
/ 13/89
/ 13/95
/ 14/19
/ 14/34
/ 631/67/1059/2326
/ 631/67/327
/ 82/1
/ Antineoplastic Agents - administration & dosage
/ Apoptosis
/ Autophagy
/ Autophagy - drug effects
/ BNIP3 protein
/ Cell death
/ Cell Hypoxia - drug effects
/ Cell Line, Tumor
/ Chemoresistance
/ Cisplatin
/ Cisplatin - administration & dosage
/ Dose-Response Relationship, Drug
/ Drug Resistance, Neoplasm - drug effects
/ Humanities and Social Sciences
/ Humans
/ Hypoxia
/ Lung cancer
/ Lung Neoplasms - drug therapy
/ Lung Neoplasms - metabolism
/ Lung Neoplasms - pathology
/ Mortality
/ multidisciplinary
/ Neoplasm Proteins - metabolism
/ Oxygen - metabolism
/ Phagocytosis
/ Science
/ siRNA
/ Solid tumors
2015
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Hypoxia-induced autophagy mediates cisplatin resistance in lung cancer cells
by
Wu, Hui-Mei
, Ding, Pei-Shan
, Jiang, Zi-Feng
, Shao, Li-Jie
, Liu, Rong-Yu
in
13/1
/ 13/109
/ 13/2
/ 13/31
/ 13/51
/ 13/89
/ 13/95
/ 14/19
/ 14/34
/ 631/67/1059/2326
/ 631/67/327
/ 82/1
/ Antineoplastic Agents - administration & dosage
/ Apoptosis
/ Autophagy
/ Autophagy - drug effects
/ BNIP3 protein
/ Cell death
/ Cell Hypoxia - drug effects
/ Cell Line, Tumor
/ Chemoresistance
/ Cisplatin
/ Cisplatin - administration & dosage
/ Dose-Response Relationship, Drug
/ Drug Resistance, Neoplasm - drug effects
/ Humanities and Social Sciences
/ Humans
/ Hypoxia
/ Lung cancer
/ Lung Neoplasms - drug therapy
/ Lung Neoplasms - metabolism
/ Lung Neoplasms - pathology
/ Mortality
/ multidisciplinary
/ Neoplasm Proteins - metabolism
/ Oxygen - metabolism
/ Phagocytosis
/ Science
/ siRNA
/ Solid tumors
2015
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Hypoxia-induced autophagy mediates cisplatin resistance in lung cancer cells
Journal Article
Hypoxia-induced autophagy mediates cisplatin resistance in lung cancer cells
2015
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Overview
Hypoxia which commonly exists in solid tumors, leads to cancer cells chemoresistance via provoking adaptive responses including autophagy. Therefore, we sought to evaluate the role of autophagy and hypoxia as well as the underlying mechanism in the cisplatin resistance of lung cancer cells. Our study demonstrated that hypoxia significantly protected A549 and SPC-A1 cells from cisplatin-induced cell death in a Hif-1α- and Hif-2α- dependent manner. Moreover, compared with normoxia, cisplatin-induced apoptosis under hypoxia was markedly reduced. However, when autophagy was inhibited by 3-MA or siRNA targeted ATG5, this reduction was effectively attenuated, which means autophagy mediates cisplatin resisitance under hypoxia. In parallel, we showed that hypoxia robustly augmented cisplatin-induced autophagy activation, accompanying by suppressing cisplatin-induced BNIP3 death pathways, which was due to the more efficient autophagic process under hypoxia. Consequently, we proposed that autophagy was a protective mechanism after cisplatin incubation under both normoxia and hypoxia. However, under normoxia, autophagy activation ‘was unable to counteract the stress induced by cisplatin, therefore resulting in cell death, whereas under hypoxia, autophagy induction was augmented that solved the cisplatin-induced stress, allowing the cells to survival. In conclusion, augmented induction of autophagy by hypoxia decreased lung cancer cells susceptibility to cisplatin-induced apoptosis.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/109
/ 13/2
/ 13/31
/ 13/51
/ 13/89
/ 13/95
/ 14/19
/ 14/34
/ 82/1
/ Antineoplastic Agents - administration & dosage
/ Cisplatin - administration & dosage
/ Dose-Response Relationship, Drug
/ Drug Resistance, Neoplasm - drug effects
/ Humanities and Social Sciences
/ Humans
/ Hypoxia
/ Lung Neoplasms - drug therapy
/ Neoplasm Proteins - metabolism
/ Science
/ siRNA
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