Abstract 2923: Glucose-regulated protein 78(GRP78) mediated the therapeutic efficacy of epirubicin via the downregulation of intracellular oxidative stress in colon cancer cells.

Abstract

Abstract Background: The 78-kDa glucose-regulated protein (GRP78) is induced in the cancer microenvironment and can be considered as a novel predictor of responsiveness to chemotherapy in many cancers. However, there is little information regarding whether the expression level of GRP78 affects epirubicin treatment in colon cancer. Methods: The expression levels of GRP78 were determined in HT-29 and DLD-1 colon cancer cells. GRP78 expression was suppressed in DLD-1 cells using a short interfering RNA (siRNA) technique. The anti-cancer effects of epirubicin were examined using a MTT assay, TUNEL assay, and cell cycle analysis. The status of intracellular reactive oxygen species (ROS) was determined. Results: In this study, we found thateEpirubicin resistance reduced in cells with suppressed GRP78, in contrast to the parental cells, as determined by survival assays. Cell cycle analysis and TUNEL assays revealed that the apoptotic cell population was increased in the GRP78 knockdown cells treated with epirubicin compared to the scrambled control cells. We found that intracellular reactive oxygen species were higher in GRP78 knockdown DLD-1 colon cancer cells compared with scrambled control cells. Treatment with epirubicin in GRP78-knockdown DLD-1 cells enhanced apoptosis and was associated with decreased production of intracellular ROS. Conclusions: In summary, our results indicate that GRP78 expression levels were highly correlated with the therapeutic efficacy to epirubicin which was associated with decreased production of intracellular ROS. Citation Format: Yu-Jia Chang, Ching-Hsein Chen, Po-Li Wei. Glucose-regulated protein 78(GRP78) mediated the therapeutic efficacy of epirubicin via the downregulation of intracellular oxidative stress in colon cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2923. doi:10.1158/1538-7445.AM2013-2923