Department of Surgery, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei, Taiwan.
J Neurooncol. 2012 Aug;109(1):23-33. doi: 10.1007/s11060-012-0871-y. Epub 2012 Apr 15.
The effects of valproic acid (VPA) on the viability, apoptosis, and invasiveness of two glioma cells (A172 and T98G) and the underlying mechanisms were studied. VPA induced cytotoxicity and apoptosis, and suppressed the invasiveness of both cells. VPA increased the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 in A172 cells, but decreased it in T98G cells. siRNA blockade of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression partially reversed VPA-mediated effects in T98G cells, but had no effect on A172 cells. VPA increased the expression of phospho-JNK1 and phospho-ERK1/2 in A172 cells, but decreased it in T98G cells. Inhibition of JNK1 and/or ERK1/2 partially reversed the VPA effects in A172 cells. In conclusion, the effects of VPA (loss of viability, increased apoptosis, and decreased invasiveness) are, at least partly, mediated through the RECK-MMPs pathway in T98G cells and the mitogen-activated protein kinase pathways in A172 cells. The action of VPA seems to be cell type-specific in glioma cells.
研究了丙戊酸（VPA）对两种神经胶质瘤细胞（A172 和 T98G）活力、凋亡和侵袭能力的影响及其潜在机制。VPA 诱导了两种细胞的细胞毒性和凋亡，并抑制了它们的侵袭能力。VPA 增加了 A172 细胞中基质金属蛋白酶-2（MMP-2）和 MMP-9 的活性，但降低了 T98G 细胞中的活性。siRNA 阻断回复诱导含 Kazal 基序的半胱氨酸丰富蛋白（RECK）的表达部分逆转了 T98G 细胞中 VPA 介导的作用，但对 A172 细胞没有影响。VPA 增加了 A172 细胞中磷酸化-JNK1 和磷酸化-ERK1/2 的表达，但降低了 T98G 细胞中的表达。JNK1 和/或 ERK1/2 的抑制部分逆转了 A172 细胞中 VPA 的作用。总之，VPA（丧失活力、增加凋亡和降低侵袭性）的作用至少部分是通过 T98G 细胞中的 RECK-MMPs 途径和 A172 细胞中的丝裂原活化蛋白激酶途径介导的。VPA 的作用在神经胶质瘤细胞中似乎是细胞类型特异性的。
