title: Unfolded Protein Response Promotes Doxorubicin-Induced Nonsmall Cell Lung Cancer Cells Apoptosis via the mTOR Pathway Inhibition.
abstract: Drug resistance is extremely common in nonsmall cell lung cancer (NSCLC) and is one of the major problems in NSCLC chemotherapy. However, the detailed mechanisms remain largely unknown. Unfolded protein response (UPR) is involved in the tumorigenesis of NSCLC. Here, the authors demonstrated that the UPR promotes poly (ADP-ribose) polymerase activation (PARP) cleavage in NSCLC cells on doxorubicin treatment, which is a hallmark of apoptosis and caspase activation. In NSCLC cells, doxorubicin treatment triggers the UPR activation, which subsequently promotes doxorubicin-mediated apoptosis. Importantly, mild endoplasmic reticulum stress precondition enhances the sensitivity of NSCLC cells to doxorubicin-initiated apoptosis. Furthermore, the eukaryotic translation initiation factor 2α (eIF2α) branch of the UPR is involved in the synergistic role of the UPR in NSCLC cell apoptosis on doxorubicin treatment. They also demonstrated that the mTOR pathway plays an essential role in synergistic induction of apoptosis by the UPR and doxorubicin in NSCLC cells. Taken together, these results provide a potential mechanism that the UPR promotes doxorubicin-induced apoptosis in NSCLC cells, at least in part, by eIF2α-mediated mTOR signal inactivation.
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Southwest Medical University , Luzhou, China .
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: 2 Department of Public Health, Southwest Medical University , Luzhou, China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Southwest Medical University , Luzhou, China .
authors.forename: Fuli
authors.initials: F
authors.lastname: Yao
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Southwest Medical University , Luzhou, China .
authors.forename: Bin
authors.initials: B
authors.lastname: Xiao
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Southwest Medical University , Luzhou, China .
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: 3 Department of Hepatobiliary Surgery of the Affiliated Hospital, Southwest Medical University , Luzhou, China .
authors.forename: Chunhong
authors.initials: C
authors.lastname: Feng
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Southwest Medical University , Luzhou, China .
authors.forename: Chunyan
authors.initials: C
authors.lastname: Duan
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Southwest Medical University , Luzhou, China .
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Southwest Medical University , Luzhou, China .
authors.forename: Youping
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Southwest Medical University , Luzhou, China .
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: 4 Department of Thoracic Surgery, Sichuan Cancer Hospital , Chengdu, China .
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Southwest Medical University , Luzhou, China .
authors.forename: Rongyang
authors.initials: R
authors.lastname: Dai
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056811:Unfolded Protein Response
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: NSCLC; apoptosis; doxorubicin; the UPR