Zhao Shiguang, Zhang Jian, Zhang Xu, Dong Xuesong, Sun Xueying
Department of Neurosurgery, The First Clinical Medical School of Harbin Medical University, Harbin, China.
Mol Biol Rep. 2008 Sep;35(3):421-9. doi: 10.1007/s11033-007-9102-6. Epub 2007 May 26.
We have previously reported that As(2)O(3) affected cell cycle progression and cyclins D1 and B1 expression in two glioma cell lines differing in p53 status (U87MG-wt; T98G-mutated). In the present study, we further demonstrated that As(2)O(3) affected proliferation, viability and apoptosis of the two cell lines in a dose- and time-dependent manner, and T98G cells were more sensitive than U87MG cells to As(2)O(3) -induced apoptosis and inhibition of proliferation and viability. We further investigated the expression profiles of genes related with apoptosis and cell cycle in the two cell lines with a human cDNA-microarray (SuperArray) spotted with 267 genes of apoptosis and cell cycle. Thirty five genes were upregulated and 15 genes downregulated at least 2-fold by As(2)O(3) in U87-MG cells; whereas, 38 genes were upregulated and 21 genes downregulated at least 2-fold in T98G cells by As(2)O(3). After As(2)O(3) treatment, p53 expression was upregulated 56.5-fold in T98G cells, but only 6.0-fold in U87MG cells. The results indicate that As(2)O(3) suppresses the growth of U87MG cells mainly by regulating expression of genes of cell cycle arrest, stress and toxicity; whereas As(2)O(3) affects T98G cells mainly by regulating expression of genes belonging to Bcl-2, tumor necrotic factor receptor and ligand families. The data may be helpful for optimizing As(2)O(3) as an anti-cancer drug in the treatment of gliomas.
我们之前报道过，三氧化二砷（As₂O₃）影响了两种p53状态不同的胶质瘤细胞系（U87MG - 野生型；T98G - 突变型）的细胞周期进程以及细胞周期蛋白D1和B1的表达。在本研究中，我们进一步证明，As₂O₃以剂量和时间依赖性方式影响这两种细胞系的增殖、活力和凋亡，并且T98G细胞比U87MG细胞对As₂O₃诱导的凋亡以及增殖和活力抑制更敏感。我们进一步用点有267个凋亡和细胞周期相关基因的人cDNA微阵列（SuperArray）研究了这两种细胞系中与凋亡和细胞周期相关的基因表达谱。在U87 - MG细胞中，As₂O₃使35个基因上调，15个基因下调至少2倍；而在T98G细胞中，As₂O₃使38个基因上调，21个基因下调至少2倍。As₂O₃处理后，p53表达在T98G细胞中上调56.5倍，但在U87MG细胞中仅上调6.0倍。结果表明，As₂O₃主要通过调节细胞周期停滞、应激和毒性相关基因的表达来抑制U87MG细胞的生长；而As₂O₃主要通过调节属于Bcl - 2、肿瘤坏死因子受体和配体家族的基因表达来影响T98G细胞。这些数据可能有助于优化将As₂O₃作为治疗胶质瘤的抗癌药物。
