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.
2014-7-2; doi:
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© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
PMID:24982359
