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Drug resistance of glioma cells induced by over-expression of HDAC1
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Abstract:
Objective:To explore the effect of histone deacetylase 1 (HDAC1) over-expression on drug resistance of glioma cells. Methods: U87MG cells were infected with a recombinant lentiviral vector pCDH-CMV-MCS-HDAC1-EF1-Puro/over-expressing HDAC1 and a control lentiviral pCDH-CMV-MCS-EF1-Puro, respectively. Cell line U87MG-HDAC1 which stably over expressing HDAC1, and control cell line U87MG-Control were selected with purine gradient concentration and identified by Western blotting. After processed with VM-26 and DDP at different concentrations assessed by MTT of the cells was evaluated by Hoechst/PI double staining assay, and the expressions of Bcl-2、Bax and Caspase-3 were examined by Western blotting.Results: Cell line U87MG-HDAC1 that stably over expressing HDAC1 was successfuly constructed. Compared with U87GM-Control group, the expression of U87MG-HDAC1 protein was significantly increased in U87MG-HDAC1 group (\[1.148±0.024\] vs \[0.580±0.003\], P<0.01). After drug treatment the survival rate of U87MG-HDAC1 cell was remarkably higher (0.1 μg/ml VM-26: \[95.57±0.45\]% vs \[68.8±149\]%, P<001)；(0.08 μg/ml DDP:\[99.20±7.4\]% vs \[72.48±2.03\]%, P<0.01); Number of apoptotic cells decreased (P<0.05); the expression of Caspase-3 protein decreased significantly (P<0.01) and the expression ratio of Bcl-2/Bax proteins was significantly enhanced (P<0.01). Conclusion: The over-expression of HDAC1 in glima cell U87MG remarkably enhance of resistance of the cells to chemotherapeutic drugs, which was may associated with the expressions of Caspase-3 and Bcl-2/Bax.
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Project Supported:
Project supported by the Youth Foundation of the National Natural Science Foundation of China（No. 30701030），and the Project of Research Foundation in Application and Frontier Technology of Tianjin City（No. 11JCYBJC14900）
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