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Targeting Ezh2 could overcome docetaxel resistance in prostate cancer cells.

ABSTRACT:

Background

Docetaxel was used to treat metastatic CRPC patients. However, Doc resistance in prostate cancer (PCa) hinders its clinical application.

Objective

To understand the underlying mechanisms by which Doc resistance is developed and to find novel therapeutic target to cure Doc resistant PCa has clinical importance.

Methods

We 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.

Results

We 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.

Conclusions

Targeting Ezh2 could overcome Doc resistance.

SUBMITTER: Qiu X

PROVIDER: S-EPMC6324167 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Targeting Ezh2 could overcome docetaxel resistance in prostate cancer cells.

Qiu Xiaofu X Wang Wei W Li Bijun B Cheng Bo B Lin Kangjian K Bai Jian J Li Huanhui H Yang Guosheng G

BMC cancer 20190108 1

<h4>Background</h4>Docetaxel was used to treat metastatic CRPC patients. However, Doc resistance in prostate cancer (PCa) hinders its clinical application.<h4>Objective</h4>To understand the underlying mechanisms by which Doc resistance is developed and to find novel therapeutic target to cure Doc resistant PCa has clinical importance.<h4>Methods</h4>We established Doc resistant cell lines and explored the role of Ezh2 in the development of Doc resistance by overexpressing its cDNA or using its ...[more]

PMID: 30621625

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