Valproic acid affected the survival and invasiveness of human glioma cells through diverse mechanisms
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- 作者：Yun Chen (12) ychen@mail.femh.org.tw
Ya-Hui Tsai (12) yahuitsai@gmail.com
Sheng-Hong Tseng (3) tsh5110@ntu.edu.tw - 关键词：Valproic acid – ; RECK – ; Invasiveness – ; Mitogen ; activated protein kinase – ; Glioma cells
- 刊名：Journal of Neuro-Oncology
- 出版年：2012
- 出版时间：August 2012
- 年：2012
- 卷：109
- 期：1
- 页码：23-33
- 全文大小：636.9 KB
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- ISSN：1573-7373
文摘
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.