PT Journal
AU Kim, M
   Park, S
   Shim, J
   Song, Y
   Yang, K
   Heo, K
TI Accumulation of low-dose BIX01294 promotes metastatic potential of U251 glioblastoma cells
SO Oncology Letters
JI Oncol Lett
PY 2017
BP 1767
EP 1774
VL 13
IS 3
DI 10.3892/ol.2017.5626
LA English
DE Bix01294; epithelial-mesenchymal transition; glioblastoma stem cells; metastasis
AB 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.
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