title: p62/SQSTM1 is involved in cisplatin resistance in human ovarian cancer cells via the Keap1-Nrf2-ARE system.
abstract: The mechanisms underlying cisplatin resistance in tumors are not fully understood. Previous studies have reported that cellular resistance to oxidative stress is accompanied by resistance to cisplatin. However, the relationship between the resistance to oxidative stress and cisplatin drug resistance in human ovarian cancer cells (HOCCs) is not clear. Here, we reveal a critical role for the multifunctional protein p62/SQSTM1 in cisplatin resistance in human ovarian cancer cells (HOCCs). p62/SQSTM1 (sequestosome 1) plays important roles in cell differentiation, proliferation and as an antiapoptotic molecule. We found that cisplatin-resistant SKOV3/DDP cells express much higher levels of p62 than do cisplatin-sensitive SKOV3 cells. The protein p62 can activate the Keap1-Nrf2-ARE signaling pathway and induce the expression of antioxidant genes in SKOV3/DDP cells. Knockdown of p62 resensitizes SKOV3/DDP cells to cisplatin. Collectively, our data indicate that cisplatin resistance in HOCCs is partially attributable to their high expression of p62, which plays an important role in preventing ROS stress-induced apoptosis by regulating the Keap1-Nrf2-ARE signaling pathway.
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Meihui
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Huimei
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, The People's Hospital of Jilin Province, Changchun, Jilin 130021, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Gu
authors.affiliation: Medical Research Lab, Jilin Medical College, Jilin 132013, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Manhua
authors.initials: M
authors.lastname: Cui
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction / Q000187:drug effects; D033921:Vesicular Transport Proteins / Q000096:biosynthesis*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000975:Antioxidants; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C115740:VPS52 protein, human; D033921:Vesicular Transport Proteins; D002945:Cisplatin