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Inhibition of hypoxia-inducible factor-1 alpha radiosensitized MG-63 human osteosarcoma cells in vitro

Abstract

Aims and background

Hypoxia is a fundamental microenvironmental component of osteosarcoma which induces activation of the hypoxia-inducible factor-1 (HIF-1) pathway. Overexpression of HIF-1α has been linked to tumor resistance to radio- or chemotherapy. However, little is known about the effects of HIF-1α inhibition on hypoxic radioresistance of human osteosarcoma cells. Here, we investigated the effects of HIF-1α inhibition on cell survival and radiosensitivity in the MG-63 human osteosarcoma cell line.

Methods

HIF-1α inhibition was achieved by small interfering RNA (siRNA) targeting of HIF-1α or via chetomin. Inhibition of the HIF-1 pathway was determined by monitoring the expression levels of HIF-1α, carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) using quantitative real-time PCR and Western blot analyses. Clonogenic assay was performed after irradiation (2-10 Gy) to investigate the effect of HIF-1α inhibition on the radiosensitivity of human osteosarcoma cells under normoxic and hypoxic conditions.

Results

Compared to the control groups, treatment with HIF-1α siRNA or chetomin significantly reduced the hypoxia-inducible radioresistance of MG-63 cells. However, siRNA and chetomin showed different effects on the radiosensitivity under normoxic conditions.

Conclusions

Our results indicate that inhibition of HIF-1α effectively decreases hypoxia-induced transcription and radiosensitizes hypoxic MG-63 human osteosarcoma cells in vitro.

Tumori 2015; 101(5): 578 - 584

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.5301/tj.5000243

Authors

Zhu Jin, Yu Aixi, Qi Baiwen, Li Zonghuan, Hu Xiang

Article History

Disclosures

Financial support: This work was supported by the National Natural Science Foundation of China (no. 81171713) and the Hubei Province Outstanding Medical Academic Leader Program.
Conflict of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the ­paper.

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Authors

Affiliations

  • Department of Micro-Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan - China

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