组蛋白修饰酶选择性抑制剂对 C6 神经胶质瘤细胞的影响。
The effects of selected inhibitors of histone modifying enzyme on C6 glioma cells.
机构信息
Laboratory of Molecular Neurobiology, Neurobiology Center, The Nencki Institute of Experimental Biology, Warszawa, Poland.
Laboratory of Molecular Neurobiology, Neurobiology Center, The Nencki Institute of Experimental Biology, Warszawa, Poland.
出版信息
Pharmacol Rep. 2014 Feb;66(1):107-13. doi: 10.1016/j.pharep.2013.08.011. Epub 2014 Feb 1.
BACKGROUND
Aberrant epigenetic histone modifications are implicated in cancer pathobiology, therefore histone modifying enzymes are emerging targets for anti-cancer therapy. There is a few evidence for deregulation of the histone modifying enzymes in glioblastomas. Glioma treatment is a clinical challenge due to its resistance to current therapies.
METHODS
The effect of selected inhibitors on epigenetic modifications and viability of glioma C6 cells were studied using immunofluorescence and MTT metabolism test.
RESULTS
We found that VPA and TSA increase histone H4 acetylation in glioma cells, while chaetocin and BIX01294 at low concentrations reduce H3K9me3, and 3DZNep decreases H3K27me3. Long-term treatment with some epigenetic inhibitors affects viability of glioma cells.
CONCLUSIONS
We established the concentrations of selected inhibitors which in C6 glioma cells inhibit the enzyme activity, but do not decrease cell viability, hence allow to study the role of histone modifications in C6 glioma biology.
背景
异常的表观遗传组蛋白修饰与癌症的病理生物学有关，因此组蛋白修饰酶是抗癌治疗的新兴靶点。在神经胶质瘤中，组蛋白修饰酶的失调有一些证据。由于对当前疗法的耐药性，胶质瘤的治疗是一个临床挑战。
方法
使用免疫荧光和 MTT 代谢试验研究了选定抑制剂对神经胶质瘤 C6 细胞的表观遗传修饰和活力的影响。
结果
我们发现 VPA 和 TSA 增加了神经胶质瘤细胞中的组蛋白 H4 乙酰化，而低浓度的 chaetocin 和 BIX01294 减少了 H3K9me3，3DZNep 减少了 H3K27me3。一些表观遗传抑制剂的长期治疗会影响神经胶质瘤细胞的活力。
结论
我们确定了选定抑制剂在 C6 神经胶质瘤细胞中的浓度，这些浓度抑制酶活性，但不会降低细胞活力，因此可以研究组蛋白修饰在 C6 神经胶质瘤生物学中的作用。
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