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Abstract

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, β-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.

Author information

Kim MY1,2, Park SJ1, Shim JW1, Song YJ1, Yang K1,3,4, Park SJ1, Heo K1.

1Research Center, Dongnam Institute of Radiological and Medical Science (DIRAMS), Busan 619-953, Republic of Korea.2Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.3Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences (DIRAMS), Busan 619-953, Republic of Korea.4Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 13557, Republic of Korea.