title: ER stress and autophagy are involved in the apoptosis induced by cisplatin in human lung cancer cells.
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.
authors.affiliation: Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Shaomin
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Bingdi
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.affiliation: Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Zhongsen
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000072283:A549 Cells; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial
chemical_list: D000970:Antineoplastic Agents; C025946:3-methyladenine; D002738:Chloroquine; D000225:Adenine; D002945:Cisplatin