Knockdown of TRAP1 promotes cisplatin-induced apoptosis by promoting the ROS-dependent mitochondrial dysfunction in lung
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Knockdown of TRAP1 promotes cisplatin-induced apoptosis by promoting the ROS-dependent mitochondrial dysfunction in lung cancer cells Xiaowei Zhang1 · Yu Dong2 · Miao Gao3 · Minfeng Hao4 · Hui Ren5 · Ling Guo6 · Hua Guo2 Received: 15 May 2020 / Accepted: 6 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The tumor necrosis factor receptor-associated protein 1 (TRAP1) is associated with the occurrence and development of various diseases, including inflammation and cancer. However, the role and mechanism of TRAP1 in the development of lung cancer need to be further explored. Therefore, the purpose of this study is to investigate the role of TRAP1 in the regulation of apoptosis by cisplatin and its special mechanism. The RT-qPCR and Western blot were used to detect the mRNA and protein expression of ANGPTL4 in A549 and H1299 cells, respectively. And the cell apoptosis and cell cycle were measured by flow cytometry (FCM). The expression of genes related to apoptosis and drug resistance as well as the cell cycle regulators, including MDM2, CyclinB1, and CDK1, were detected by Western blot. Finally, the reactive oxygen species (ROS) indicator DCFH-DA was performed to detect the generation of ROS, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. The results showed that the expression of TRAP1 was significantly increased in A549/DDP and H1299/DDP than A549 and H1299 cells. Further research found that knockdown of TRAP1 induced apoptosis and caused G2/M cell cycle arrest in A549/DDP and H1299/DDP cells. What is more, siTRAP1 reduced the relative JC-1 polymer monomer fluorescence ratio and decreased the ΔΨm, up-regulated the expression of Cytochrome C. Importantly, siTRAP1 induces ROS-dependent mitochondrial dysfunction. It is suggested that that TRAP1 suppresses cisplatin-induced apoptosis by promoting ROS-dependent mitochondrial dysfunction. Keywords TRAP1 · Drug resistance · Apoptosis · ROS · Lung cancer
* Hua Guo [email protected] 1
Department of Oncology, Xi’an Central Hospital, The Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xi’an 710003, Shaanxi, China
2
Department of Respiratory, Xi’an Central Hospital, The Affiliated Hospital of Xian Jiaotong University College of Medicine, 185 Houzai Men, Xi’an 710003, Shaanxi, China
3
Department of Obstetrics and Gynecology, Xi’an No.5 Hospital, Xi’an 710082, Shaanxi, China
4
Department of Neurology, Xi’an Central Hospital, The Affiliated Hospital of Xian Jiaotong University College of Medicine, Xi’an 710003, Shaanxi, China
5
Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
6
Yan’an University College of Medicine, Yan’an 716000, Shaanxi, China
Introduction Lung cancer is one of the most dangerous diseases threatening people’s lives worldwide. According to the statistics, approximately 80% of lung cancers are non-small cell lung carcinoma (NSCLC), and the remaining 20%
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