靶向 Ezh2 可以克服前列腺癌细胞对多西他赛的耐药性。
Targeting Ezh2 could overcome docetaxel resistance in prostate cancer cells.
机构信息
Department of Urology, Southern Medical University Third Medical College, Guangzhou, 510317, China.
Department of Urology, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China.
出版信息
BMC Cancer. 2019 Jan 8;19(1):27. doi: 10.1186/s12885-018-5228-2.
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.
背景
多西紫杉醇被用于治疗转移性去势抵抗性前列腺癌（CRPC）患者。然而，前列腺癌中的多西紫杉醇耐药（Doc 耐药）阻碍了其临床应用。
目的
了解 Doc 耐药发展的潜在机制，并找到治疗 Doc 耐药前列腺癌的新治疗靶点，这具有重要的临床意义。
方法
我们建立了 Doc 耐药细胞系，并通过过表达其 cDNA 或使用其抑制剂来探索 Ezh2 在 Doc 耐药发展中的作用。
结果
我们发现，在我们建立的 Doc 耐药（DocR）细胞中诱导了 Ezh2，这归因于 miR-101-3p 和 miR-138-5p 的沉默表达。通过抑制剂或 miRNA 模拟物阻断 Ezh2 活性可以通过抑制 Doc 诱导的癌症干细胞群来克服 Doc 耐药。在机制上，Ezh2 活性对于 Doc 处理后 Nanog、Sox2 和 CD44 的诱导表达是必需的。
结论
靶向 Ezh2 可以克服 Doc 耐药。
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