title: GRP78 up-regulation leads to hypersensitization to cisplatin in A549 lung cancer cells.
abstract: BACKGROUND
  GRP78 is one of the stress proteins linked to different functions in the cell. Previous reports have shown opposing functions of GRP78 in relation to drug resistance/sensitivity. In the current study, we examined the role of GRP78 in cisplatin-treated A549 cells.
  
  
  METHODS
  GRP78 was over-expressed in A549 cells with 2-deoxyglucose (2-dG) or tunicamycin (TM) treatments for 48 h and subsequently exposed to cisplatin for 2 h. Viability of these cells was determined at 0, 12, 24, 36 and 48 h afterwards.
  
  
  RESULTS
  We showed that A549 cells are hypersensitized to cisplatin following a transient GRP78 up-regulation. This hypersensitization is caused by the activation of JNK pathway and NF-κB, leading to early onset of apoptosis.
  
  
  CONCLUSIONS
  Induction of GRP78 can be used as a potential tool to overcome drug resistance in lung cancer cells.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND, U.S.A. Department of Hematology/Oncology, School of Medicine, Case Western Reserve University, Cleveland, OH, U.S.A. mohammadahmad2005@gmail.com.
authors: Mohammad
authors: M
authors: Ahmad
authors: Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, U.S.A.
authors: Insu Frank
authors: IF
authors: Hahn
authors: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, ND, U.S.A. Department of Hematology/Oncology, School of Medicine, Case Western Reserve University, Cleveland, OH, U.S.A.
authors: Satadal
authors: S
authors: Chatterjee
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D016328:NF-kappa B; D014415:Tunicamycin; D003847:Deoxyglucose; D048031:JNK Mitogen-Activated Protein Kinases; D002945:Cisplatin
keywords: Apoptosis; ER stress; GRP78; NF-κB; c-Jun; cell cycle; cisplatin