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Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status

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Abstract

We have previously reported that As2O3 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 As2O3 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 As2O3 -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 As2O3 in U87-MG cells; whereas, 38 genes were upregulated and 21 genes downregulated at least 2-fold in T98G cells by As2O3. After As2O3 treatment, p53 expression was upregulated 56.5-fold in T98G cells, but only 6.0-fold in U87MG cells. The results indicate that As2O3 suppresses the growth of U87MG cells mainly by regulating expression of genes of cell cycle arrest, stress and toxicity; whereas As2O3 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 As2O3 as an anti-cancer drug in the treatment of gliomas.

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Acknowledgements

This work was supported in part by the National Natural Scientific Foundation of China (30471681, 30571808). Zhao S and Zhang J contributed equally to this work.

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Authors and Affiliations

  1. Department of Neurosurgery, The First Clinical Medical School of Harbin Medical University, Harbin, 150001, China

    Shiguang Zhao & Xu Zhang

  2. Hepatosplenic Surgery Center/Department of General Surgery, First Clinical Medical School of Harbin Medical University, Harbin, 150001, China

    Jian Zhang, Xuesong Dong & Xueying Sun

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  1. Shiguang Zhao
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  2. Jian Zhang
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  3. Xu Zhang
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  4. Xuesong Dong
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  5. Xueying Sun
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Correspondence to Xueying Sun.

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Zhao, S., Zhang, J., Zhang, X. et al. Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep 35, 421–429 (2008). https://doi.org/10.1007/s11033-007-9102-6

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  • DOI: https://doi.org/10.1007/s11033-007-9102-6

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