Three-dimensional culture sensitizes epithelial ovarian cancer cells to EZH2 methyltransferase inhibition.

作者: Michael Amatangelo , Azat Garipov , Hua Li , Jose R. Conejo-Garcia , David Speicher

DOI: 10.4161/CC.25163

关键词: Tumor microenvironmentEnzymeMethyltransferaseEZH2B-cell lymphomaCell cultureMatrigelCancer researchApoptosisBiology

摘要: Inhibitors of EZH2 methyltransferase activity have been demonstrated to selectively suppress the growth diffused large B cell lymphoma (DLBCL) cells with gain-of-function mutations in EZH2, while exhibiting very limited effects on DLBCL wild-type EZH2. Given that is often overexpressed but not mutated solid tumors, it important investigate determinants sensitivity tumor inhibitors. In current study, we show three-dimensional (3D) culture epithelial ovarian cancer (EOC) overexpress sensitizes these inhibition. Treatment EOC GSK343, a specific inhibitor methyltransferase, decreases level H3K27Me3, product EZH2’s enzymatic activity. However, GSK343 exhibited conventional two-dimensional (2D) culture. contrast, significantly suppressed cultured 3D matrigel extrac...

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