GRP78 regulates sensitivity of human colorectal cancer cells to DNA targeting agents

This study was carried out to investigate the activation status of unfolded protein response (UPR) in colorectal cancer (CRC) and its contribution to CRC resistance to chemotherapy-induced apoptosis. Chemotherapy-induced apoptosis was assessed by the propidium iodide method. Activation of UPR was ev...

Full description

Saved in:
Bibliographic Details
Published in:Cytotechnology (Dordrecht) 2016-05, Vol.68 (3), p.459-467
Main Authors: Mhaidat, Nizar M., Alzoubi, Karem H., Khabour, Omar F., Banihani, Mohammed N., Al-Balas, Qosay A., Swaidan, Sulaiman
Format: Article
Language:English
Subjects:
Apoptosis
Biochemistry
Biomedicine
Biotechnology
Cancer therapies
Chemistry
Chemistry and Materials Science
Chemotherapy
Cisplatin
Colorectal cancer
Colorectal carcinoma
Immunoblotting
Immunohistochemistry
Kinases
mRNA
Original Research
Propidium iodide
Protein folding
siRNA
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This study was carried out to investigate the activation status of unfolded protein response (UPR) in colorectal cancer (CRC) and its contribution to CRC resistance to chemotherapy-induced apoptosis. Chemotherapy-induced apoptosis was assessed by the propidium iodide method. Activation of UPR was evaluated in CRC cell lines using immunoblotting technique and in CRC tissues using immunohistochemistry. Findings of the present study revealed that the UPR is constitutively activated in CRC cell lines and CRC tissues isolated from patients, as evidenced by relatively high levels of the 78-kDa glucose-regulated protein (GRP78) and spliced X-box-binding protein 1 mRNA in tissue samples. In addition, CRC cell lines differentially responded to clinically relevant DNA-targeting agents including cisplatin, and 5-flourouracil. Moreover, the levels of GRP78 were inversely associated with sensitivity of CRC cells to chemotherapy-induced apoptosis. Inhibition of GRP78 by siRNA resulted in increased sensitivity of CRC cells to chemotherapeutic agents. Collectively, current results appear to provide novel insights into the role of UPR in determining sensitivity of CRC cells to chemotherapeutic agents and might have important implications for personalized CRC treatment.
ISSN:0920-9069
1573-0778
DOI:10.1007/s10616-014-9799-8