Glioma is a highly malignant type of intracranial tumor with a poor prognosis resulting from traditional chemo-resistance with temozolomide (TMZ). Luteolin has been detected to exert limited anti-tumor effects on gliomas, while valproic acid (VPA) is a common chemotherapy sensitizer in the treatment of tumors. In this study, three glioma cell lines including U251, LN229 and SNB19 were selected for evaluation of combined anti-tumor effects of VPA and luteolin via Cell Counting Kit-8 (CCK-8) assay, colony formation assay, wound-healing assay, flow cytometry and western blot assay. The results disclosed that VPA sensitized glioma cells to luteolin by repressing cell viability, colony formation and migration. Mechanically, VPA boosted cellular apoptosis and cell-cycle arrest by increased level of cleaved caspase-3/caspase-3, cleaved PARP/PARP and Bax/Bcl-2. In addition, VPA also facilitated cellular autophagy via the decline of p62, p-Akt/Akt and the accumulation of LC3-II. These findings suggested that VPA enhanced the anticancer effects of luteolin by strengthening apoptosis and autophagy via Akt signaling, which could be adopted as a novel therapy for glioma.

胶质瘤是一种高度恶性的颅内肿瘤，由于对替莫唑胺（TMZ）的传统化疗耐药，预后较差。已检测到木犀草素对神经胶质瘤发挥有限的抗肿瘤作用，而丙戊酸 (VPA) 是治疗肿瘤的常见化疗增敏剂。在本研究中，选择 U251、LN229 和 SNB19 三种胶质瘤细胞系，通过细胞计数试剂盒 8 (CCK-8) 测定、集落形成测定、伤口愈合测定、流式细胞术和蛋白质印迹分析。结果表明，VPA 通过抑制细胞活力、集落形成和迁移使神经胶质瘤细胞对木犀草素敏感。机械地，VPA 通过增加裂解的 caspase-3/caspase-3 水平来促进细胞凋亡和细胞周期停滞，裂解的 PARP/PARP 和 Bax/Bcl-2。此外，VPA 还通过 p62、p-Akt/Akt 的下降和 LC3-II 的积累促进细胞自噬。这些发现表明，VPA通过Akt信号增强细胞凋亡和自噬，增强了木犀草素的抗癌作用，可作为胶质瘤的新疗法。