Autophagy inhibitor chloroquine induces apoptosis of cholangiocarcinoma cells via endoplasmic reticulum stress

Jia,Baoxing; Xue,Yanan; Yan,Xiaoyu; Li,Jiuling; Wu,Yao; Guo,Rui; Zhang,Juanjuan; Zhang,Lichao; Li,Yaping; Liu,Yahui; Sun,Liankun

doi:10.3892/ol.2018.9131

Autophagy inhibitor chloroquine induces apoptosis of cholangiocarcinoma cells via endoplasmic reticulum stress

Authors:
- Baoxing Jia
- Yanan Xue
- Xiaoyu Yan
- Jiuling Li
- Yao Wu
- Rui Guo
- Juanjuan Zhang
- Lichao Zhang
- Yaping Li
- Yahui Liu
- Liankun Sun
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Affiliations: Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Dermatology, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China, Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: July 11, 2018 https://doi.org/10.3892/ol.2018.9131
Pages: 3509-3516
Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Poor prognosis and chemotherapy tolerance are the main obstacles encountered in the treatment of cholangiocarcinoma. Chloroquine (CQ), an antimalarial agent, is able to induce sustained endoplasmic reticulum (ER) stress by functioning as an autophagy inhibitor. The present study indicated that CQ had the ability to induce apoptosis in QBC939 cholangiocarcinoma cells. Furthermore, using western blotting, Hoechst staining and flow cytometry, it was demonstrated that CQ induced the apoptosis of QBC939 cholangiocarcinoma cells. Analysis by a polymerase chain reaction (PCR) array and confirmation via quantitative PCR technology indicated that the expression levels of growth arrest and DNA damage 153 [C/EBP homologous protein (CHOP)], a key molecule involved in ER stress‑induced apoptosis, and its downstream death receptors were increased following CQ stimulation. It was considered that the upregulation of CHOP may mediate CQ‑induced extrinsic pathways and autophagy‑dependent apoptosis; therefore, the role of autophagy in cholangiocarcinoma treatment was elucidated based on the data demonstrating that CQ regulates the ER‑autophagy network in tumor cells. Furthermore, it was considered that CQ may become a novel and effective strategy for the treatment of cholangiocarcinoma.

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