ZEB1 Promotes Chemoresistance to Cisplatin in Ovarian Cancer Cells by Suppressing SLC3A2

被引：42
作者：
Cui, Yajie [1 ]
Qin, Li [2 ]
Tian, Defu [3 ,4 ]
Wang, Ting
Fan, Lijing [5 ]
Zhang, Peilian [5 ]
Wang, Zhongqi [6 ]
机构：
[1] Xian 4 Hosp, Dept Obstet & Gynecol, Xian, Shaanxi, Peoples R China
[2] Shaanxi Prov Peoples Hosp, Dept Obstet & Gynecol, Xian, Shaanxi, Peoples R China
[3] Shaanxi Prov Fourth Peoples Hosp, Dept Gen Surg, Xian, Shaanxi, Peoples R China
[4] Northwest Women & Childrens Hosp, Xian, Shaanxi, Peoples R China
[5] Xian 1 Hosp, Dept Obstet & Gynecol, Xian, Shaanxi, Peoples R China
[6] An Kang Cent Hosp, Dept Gynecol, An Kang 725000, Peoples R China
来源：
CHEMOTHERAPY | 2018年 / 63卷 / 05期
关键词：
Ovarian cancer; ZEB1; SLC3A2; Chemoresistance; Apoptosis; Metastasis; MESENCHYMAL TRANSITION; DRUG-RESISTANCE; DOWN-REGULATION; CD98HC SLC3A2; CONTRIBUTES; PROLIFERATION; PACLITAXEL; EXPRESSION; PATHWAY; GROWTH;
D O I：
10.1159/000493864
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Ovarian cancer is one of the deadliest gynecological malignancies in women. Chemoresistance has been a major obstacle for ovarian cancer treatment. Zinc finger E-box-binding homeobox 1 (ZEB1) is an important regulator of tumor development in various types of cancer. Abnormal expression of SLC3A2 (CD98hc), a type 2 transmembrane cell surface molecule, has been described in several cancers. This study was designed to investigate the role of ZEB1 and SLC3A2 in the chemoresistance to cisplatin in ovarian cancer cells. We found that ZEB1 was increased in cisplatin-resistant SKOV3/DPP cells. Downregulation of ZEB1 significantly decreased cell viability in response to cisplatin, increased cisplatin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. In addition, downregulation of ZEB1 decreased the volume and weight of implanted tumors. SLC3A2 was decreased in cisplatin-resistant SKOV3/DPP cells. Upregulation of SLC3A2 significantly decreased cell viability in response to cisplatin, increased cisplatin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. Moreover, upregulation of SLC3A2 decreased the volume and weight of implanted tumors. Downregulation of ZEB1 resulted in a significant increase of SLC3A2 expression. Moreover, downregulation of SLC3A2 significantly inhibited ZEB1 knockdown-mediated inhibition of cisplatin-resistance. ZEB1-mediated regulation of SLC3A2 was involved in the chemoresistance to cisplatin in ovarian cancer cells. Overall, we provide new insights into the mechanism of chemoresistance to cisplatin in ovarian cancer cells. ZEB1/SLC3A2 may be promising therapeutic targets for enhancement of the sensitivity of ovarian cancer cells to cisplatin-mediated chemotherapy. (C) 2018 S. Karger AG, Basel
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收藏
页码：262 / 271
页数：10
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