Accumulation of low-dose BIX01294 promotes metastatic potential of U251 glioblastoma cells

作者：Kim Min Young; Park Shin Ji; Shim Jae Woong; Song Yu Jin; Yang Kwangmo; Park Seong Joon; Heo Kyu

来源：Oncology Letters, 2017, 13(3): 1767-1774.

DOI：10.3892/ol.2017.5626

• BIX01294
• metastasis
• epithelial-mesenchymal transition
• glioblastoma stem cells

BIX01294 (Bix) is known to be a euchromatic histone-lysine N-methyltransferase 2 inhibitor and treatment with Bix suppresses cancer cell survival and proliferation. In the present study, it was observed that sequential treatment with low-dose Bix notably increases glioblastoma cell migration and metastasis. It was demonstrated that U251 cells sequentially treated with low-dose Bix exhibited induced characteristic changes in critical epithelial-mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, beta-catenin and zinc finger protein SNAI2. Notably, sequential treatment with Bix also increased the expression of cancer stem cell-associated markers, including sex determining region Y-box 2, octamer-binding transcription factor 4 and cluster of differentiation 133. Neurosphere formation was significantly enhanced in cells sequentially treated with Bix, compared with control cells ( control: P=0.011; single treatment of Bix, P=0.045). The results of the present study suggest that accumulation of low-dose Bix enhanced the migration and metastatic potential of glioblastoma cells by regulating EMT-associated gene expression, which may be the cause of the altered properties of glioblastoma stem cells.

• 出版日期2017-3