Targeting Ezh2 could overcome docetaxel resistance in prostate cancer cells

被引：28
作者：
Qiu, Xiaofu [1 ,5 ]
Wang, Wei [2 ]
Li, Bijun [3 ]
Cheng, Bo [4 ]
Lin, Kangjian [1 ]
Bai, Jian [5 ]
Li, Huanhui [5 ]
Yang, Guosheng [1 ,5 ]
机构：
[1] Southern Med Univ, Dept Urol, Med Coll 3, Guangzhou 510317, Guangdong, Peoples R China
[2] Guangzhou Mil Command, Dept Urol, Guangzhou Gen Hosp, Guangzhou 510515, Guangdong, Peoples R China
[3] Guangdong Med Coll, Dept Urol, Affiliated Hosp 2, Zhanjiang 524003, Peoples R China
[4] Southwest Med Univ, Dept Urol, Affiliated Hosp, Luzhou 646000, Peoples R China
[5] Guangdong Second Prov Gen Hosp, Dept Urol, Guangzhou 510317, Guangdong, Peoples R China
来源：
BMC CANCER | 2019年 / 19卷 / 1期
关键词：
ANDROGEN RECEPTOR; MITOTIC CATASTROPHE; EXPRESSION; CHEMOTHERAPY; THERAPY; BREAST;
D O I：
10.1186/s12885-018-5228-2
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
BackgroundDocetaxel was used to treat metastatic CRPC patients. However, Doc resistance in prostate cancer (PCa) hinders its clinical application.ObjectiveTo understand the underlying mechanisms by which Doc resistance is developed and to find novel therapeutic target to cure Doc resistant PCa has clinical importance.MethodsWe established Doc resistant cell lines and explored the role of Ezh2 in the development of Doc resistance by overexpressing its cDNA or using its inhibitor.ResultsWe found that Ezh2 was induced in our established Doc resistant (DocR) cells, which was attributable to the silenced expression of miR-101-3p and miR-138-5p. Blockage of Ezh2 activity by either inhibitor or miRNA mimics could overcome Doc resistance by suppressing Doc-induced cancer stem cells populations. Mechanistically, Ezh2 activity was required for the induced expression of Nanog, Sox2 and CD44 upon Doc treatment.ConclusionsTargeting Ezh2 could overcome Doc resistance.
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页数：8
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