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Anticancer Res. 2014 Jul;34(7):3493-500.

GRP78 up-regulation leads to hypersensitization to cisplatin in A549 lung cancer cells.

Author information

  • 1Department 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.
  • 2Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, U.S.A.
  • 3Department 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.

KEYWORDS:

Apoptosis; ER stress; GRP78; NF-κB; c-Jun; cell cycle; cisplatin

PMID:
24982359
[PubMed - indexed for MEDLINE]
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