膠芽腫は予後不良な悪性脳腫瘍であり、膠芽腫幹細胞に対する治療が再発予防や根治性の向上に重要とされている。本研究では、9種類の膠芽腫患者由来膠芽腫幹細胞に対しNotch阻害剤MRK-003の有効性を評価した。MRK-003は全ての膠芽腫幹細胞に対し、細胞増殖抑制、アポトーシス促進、幹細胞形質抑制の効果を示した。使用した膠芽腫幹細胞は高感受性群と低感受性群に分けられた。IC50(50%阻害濃度)はCD44の発現量と負の相関関係、CD133の発現量と正の相関関係を認めた。MRK-003はCD44高値、CD133低値の膠芽腫幹細胞に有効であることが示唆された。
Glioblastoma is the most malignant primary brain tumor in humans. The patients with glioblastoma have a uniformly poor prognosis. The significance of targeting glioblastoma-initiating cells (GICs) may be important for successful treatment of glioblastoma. In this study, we analyzed the effect of the Notch inhibitor MRK-003 on nine patient-derived GICs. MRK-003 suppressed GIC's proliferation and stemness maintenance, and promoted their apoptosis. Based on their sensitivities to MRK-003, the nine GICs were divided into “relatively sensitive” and “relatively resistant” GICs. The IC50(half maximal inhibitory concentration) of MRK003 in a set of GICs exhibited a negative correlation with CD44 and positive correlation with CD133. Our study suggested that MRK-003 may exhibit significant therapeutic potential for GICs with CD44-high and CD133-low expression.