Mohammad Ahmad1, Insu Frank Hahn2, Satadal Chatterjee3. 1. 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. 2. Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, U.S.A. 3. 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.
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. MATERIALS AND 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. CONCLUSION: Induction of GRP78 can be used as a potential tool to overcome drug resistance in lung cancer cells. Copyright
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. MATERIALS AND 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. CONCLUSION: Induction of GRP78 can be used as a potential tool to overcome drug resistance in lung cancer cells. Copyright
Authors: Stefan Tenzer; Petra Leidinger; Christina Backes; Hanno Huwer; Andreas Hildebrandt; Hans-Peter Lenhof; Tanja Wesse; Andre Franke; Eckart Meese; Andreas Keller Journal: Oncotarget Date: 2016-03-22