p62/SQSTM1 is involved in cisplatin resistance in human ovarian cancer cells via the Keap1-Nrf2-ARE system

被引：74
作者：
Xia, Meihui [1 ,2 ]
Yu, Huimei [3 ]
Gu, Shuang [4 ]
Xu, Ye [5 ]
Su, Jing [3 ]
Li, Hongyan [3 ]
Kang, Jinsong [3 ]
Cui, Manhua [1 ]
机构：
[1] Jilin Univ, Hosp 2, Dept Obstet & Gynecol, Changchun 130041, Jilin, Peoples R China
[2] Jilin Univ, Hosp 1, Dept Obstet & Gynecol, Changchun 130021, Jilin, Peoples R China
[3] Jilin Univ, Sch Basic Med Sci, Dept Pathophysiol, Changchun 130021, Jilin, Peoples R China
[4] Peoples Hosp Jilin Prov, Dept Thorac Surg, Changchun 130021, Jilin, Peoples R China
[5] Jilin Med Coll, Med Res Lab, Jilin 132013, Peoples R China
来源：
INTERNATIONAL JOURNAL OF ONCOLOGY | 2014年 / 45卷 / 06期
基金：
中国国家自然科学基金;
关键词：
p62/SQSTM1; Keapl-Nrf2-ARE signaling pathway; apoptosis; cisplatin; drug resistance; ovarian cancer; MOLECULAR-MECHANISMS; SIGNALING PATHWAY; OXIDATIVE STRESS; NRF2; CHEMOTHERAPY; P62;
D O I：
10.3892/ijo.2014.2669
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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 Keapl-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 Keapl-Nrf2-ARE signaling pathway.
引用
收藏
页码：2341 / 2348
页数：8
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