GRP78 Regulates Sensitivity of Human Colorectal Cancer Cells to DNA Targeting Agents

Overview

Journal Cytotechnology

Specialties Biotechnology
Genetics

Date 2014 Nov 17

PMID 25399254

Citations 16

Authors

Nizar M Mhaidat

Karem H Alzoubi

Omar F Khabour

Mohammed N Banihani

Qosay A Al-Balas

Sulaiman Swaidan

Affiliations

Soon will be listed here.

Abstract

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.

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