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.
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.
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.
Our results indicate that inhibition of HIF-1α effectively decreases hypoxia-induced transcription and radiosensitizes hypoxic MG-63 human osteosarcoma cells
Tumori 2015; 101(5): 578 - 584
Article Type: ORIGINAL RESEARCH ARTICLE
AuthorsZhu Jin, Yu Aixi, Qi Baiwen, Li Zonghuan, Hu Xiang
- • Accepted on 31/12/2014
- • Available online on 04/08/2015
- • Published in print on 09/09/2015
This article is available as full text PDF.
- Jin, Zhu [PubMed] [Google Scholar]
- Aixi, Yu [PubMed] [Google Scholar] , * Corresponding Author (firstname.lastname@example.org)
- Baiwen, Qi [PubMed] [Google Scholar]
- Zonghuan, Li [PubMed] [Google Scholar]
- Xiang, Hu [PubMed] [Google Scholar]
Department of Micro-Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan - China