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Effect of Hypoxia-inducible Factor-1α Silencing on the Sensitivity of Human Brain Glioma Cells to Doxorubicin and Etoposide

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Abstract

Multidrug resistance (MDR) is a significant problem underlying the poor prognosis associated with gliomas. Hypoxia-inducible factor-1α (HIF-1α) is thought to induce the genes expression involved in MDR. To evaluate the effect of silencing HIF-1α in human glioma T98G cells, cells were transfected with HIF-1α-small interference RNA (HIF-1α-siRNA) and cultured under hypoxic conditions. The effect of HIF-1α-siRNA on HIF-1α and multidrug resistance-associated protein 1 gene (MRP1) and protein levels was determined. Silencing rates of HIF-1α were 90%, 85%, and 88% at 24, 48, 72 h post-transfection, respectively. Corresponding rates of HIF-1α protein were 74.5%, 61.1% and 59.1%. MRP1 protein levels decreased by 7.6%, 36.8% and 45.2%. HIF-1α-siRNA transfected cells were significantly more sensitive to doxorubicin and etoposide compared to non-transfected cells. These findings suggest that the HIF-1α plays a role in mediating chemotherapeutic drug resistance in glioma cells. HIF-1α silencing may prove to be an effective therapeutic means of treating gliomas.

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Acknowledgments

This study was supported by the Country Natural Science Fund and West China Hospital.

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Authors and Affiliations

  1. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China

    Lei Chen & Dong Zhou

  2. Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China

    Peimin Feng

  3. Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China

    Shengfu Li, Dan Long, Jingqiu Cheng & Yanrong Lu

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  1. Lei Chen
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  2. Peimin Feng
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  3. Shengfu Li
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  4. Dan Long
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  5. Jingqiu Cheng
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  6. Yanrong Lu
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  7. Dong Zhou
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Correspondence to Dong Zhou.

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Chen, L., Feng, P., Li, S. et al. Effect of Hypoxia-inducible Factor-1α Silencing on the Sensitivity of Human Brain Glioma Cells to Doxorubicin and Etoposide. Neurochem Res 34, 984–990 (2009). https://doi.org/10.1007/s11064-008-9864-9

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  • DOI: https://doi.org/10.1007/s11064-008-9864-9

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