多柔比星诱导神经胶质瘤细胞凋亡需要 NFAT3。
Doxorubicin-mediated apoptosis in glioma cells requires NFAT3.
机构信息
Department of Cancer Biology and Pharmacology, College of Medicine at Peoria, University of Illinois, 1649 Peoria, IL 61656, USA.
出版信息
Cell Mol Life Sci. 2009 Dec;66(24):3967-78. doi: 10.1007/s00018-009-0157-5. Epub 2009 Sep 27.
Abstract
Nuclear factor of activated T cells (NFAT), a family of transcription factors, has been implicated in many cellular processes, including some cancers. Here, we characterize, for the first time, the role of NFAT3 in doxorubicin (DOX)-mediated apoptosis, migration, and invasion in SNB19 and U87 glioma cells. This study demonstrates that the specific knockdown of NFAT3 results in a dramatic inhibition of the apoptotic effect induced by DOX and favors cell survival. Inhibition of NFAT3 activation by shNFAT3 (shNF3) significantly downregulated tumor necrosis factor (TNF)-alpha induction, its receptor TNFR1, caspase 10, caspase 3, and poly (ADP-ribose) polymerase, abrogating DOX-mediated apoptosis in glioma cells. DOX treatment resulted in NFAT3 translocation to the nucleus. Similarly, shNF3 treatment in SNB19 and U87 cells reversed DOX-induced inhibition of cell migration and invasion, as determined by wound healing and matrigel invasion assays. Taken together, these results indicate that NFAT3 is a prerequisite for the induction of DOX-mediated apoptosis in glioma cells.
摘要
活化 T 细胞核因子（NFAT）是一类转录因子，与多种细胞过程相关，包括一些癌症。在这里，我们首次描述了 NFAT3 在阿霉素（DOX）介导的 SNB19 和 U87 神经胶质瘤细胞凋亡、迁移和侵袭中的作用。本研究表明，NFAT3 的特异性敲低导致 DOX 诱导的凋亡作用显著抑制，并有利于细胞存活。通过 shNFAT3（shNF3）抑制 NFAT3 激活显著下调肿瘤坏死因子（TNF）-α诱导、其受体 TNFR1、半胱天冬酶 10、半胱天冬酶 3 和多聚（ADP-核糖）聚合酶，从而阻断 DOX 介导的神经胶质瘤细胞凋亡。DOX 处理导致 NFAT3 易位到细胞核。同样，在 SNB19 和 U87 细胞中，shNF3 处理逆转了 DOX 诱导的细胞迁移和侵袭抑制，通过划痕愈合和基质胶侵袭实验确定。综上所述，这些结果表明 NFAT3 是 DOX 介导的神经胶质瘤细胞凋亡诱导的必要条件。
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