Chiou Hsin-Ying Clair, Lai Wen-Kuo, Huang Li-Chun, Huang Shih-Ming, Chueh Sheau-Huei, Ma Hsin-I, Hueng Dueng-Yuan
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Oncotarget. 2015 Apr 30;6(12):9959-69. doi: 10.18632/oncotarget.3692.
Although meningioma stem-like cells have been isolated and characterized, their therapeutic targeting remains a challenge. Meningioma sphere cells (MgSCs) with cancer stem cells properties show chemo- and radioresistance in comparison with meningioma adherent cells (MgACs). We tested the effect of valproic acid (VPA), a commonly used anti-epileptic drug, which passes the blood brain barrier, on cultured MgSCs. VPA reduced the viability of MgSCs and MgACs. In MgSCs, treatment with VPA increased radio-sensitivity, expression of p-cdc2, p-H2AX and cleaved caspase-3 and PARP. Anchorage-independent growth (AIG) was reduced by VPA. AIG was further reduced by combined treatment with irradiation. Expression of a stem cell marker, Oct4, was reduced by VPA. Oct4 was further decreased by combined treatment with irradiation. These results suggest that VPA may be a potential treatment for meningioma through targeting meningioma stem-like cells.
尽管脑膜瘤干细胞样细胞已被分离和鉴定，但其治疗靶点仍然是一个挑战。与脑膜瘤贴壁细胞（MgACs）相比，具有癌症干细胞特性的脑膜瘤球细胞（MgSCs）表现出化学抗性和放射抗性。我们测试了常用的抗癫痫药物丙戊酸（VPA）通过血脑屏障对培养的MgSCs的作用。VPA降低了MgSCs和MgACs的活力。在MgSCs中，VPA处理增加了放射敏感性、p-cdc2、p-H2AX和裂解的caspase-3及PARP的表达。VPA降低了非锚定依赖性生长（AIG）。联合放疗进一步降低了AIG。VPA降低了干细胞标志物Oct4的表达。联合放疗进一步降低了Oct4的表达。这些结果表明，VPA可能通过靶向脑膜瘤干细胞样细胞成为脑膜瘤的一种潜在治疗方法。
