ER stress and autophagy are involved in the apoptosis induced by cisplatin in human lung cancer cells

Shi,Shaomin; Tan,Ping; Yan,Bingdi; Gao,Rong; Zhao,Jianjun; Wang,Jing; Guo,Jia; Li,Ning; Ma,Zhongsen

doi:10.3892/or.2016.4680

ER stress and autophagy are involved in the apoptosis induced by cisplatin in human lung cancer cells

Authors:
- Shaomin Shi
- Ping Tan
- Bingdi Yan
- Rong Gao
- Jianjun Zhao
- Jing Wang
- Jia Guo
- Ning Li
- Zhongsen Ma
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Affiliations: Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China
Published online on: March 16, 2016 https://doi.org/10.3892/or.2016.4680
Pages: 2606-2614
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cisplatin [cis-diamminedichloroplatinum II (CDDP)] is one of the most classical and effective chemotherapeutic drugs for the treatment of cancers including lung cancer. However, the presence of cisplatin resistance in cancer lowers its curative effect and limits its usage in the clinic. The aim of the present study was to investigate the underlying mechanisms of cisplatin resistance in lung cancer involving endoplasmic reticulum (ER) stress and autophagy. In the present study, we detected the effect of cisplatin on cell viability, ER stress and autophagy in lung cancer cell lines A549 and H460. We also tested the effects of ER stress and autophagy on apoptosis induced by cisplatin. The results showed that cisplatin induced apoptosis, ER stress and autophagy in lung cancer cell lines. In addition, the inhibition of ER stress by 4-phenylbutyric acid (4-PBA) or tauroursodeoxycholic acid sodium (TUDC) enhanced cisplatin-induced apoptosis in the human lung cancer cells. Meanwhile, combination treatment with the autophagic inhibitor 3-methyladenine (3-MA) or chloroquine (CQ) further increased the apoptosis induced by cisplatin in the human lung cancer cells. The present study provides a novel treatment strategy - cisplatin in combination with an autophagic inhibitor or an ER stress inhibitor leads to increased apoptosis in human lung cancer cells.

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