HIF-1α inhibition by siRNA or chetomin in human malignant glioma cells: effects on hypoxic radioresistance and monitoring via CA9 expression

BMC Cancer

Research Article

Dirk Vordermark¹  Swetlana Rot¹  Matthias Bache¹  Antje Hahnel¹  Jacqueline Kessler¹  Henri Wichmann¹  Matthias Kappler¹ 

[1] Department of Radiotherapy, Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, 06097, Halle (Saale), Germany;

关键词: Glioma Cell;    Hypoxic Condition;    Malignant Glioma;    Glioma Cell Line;    Normoxic Condition;   

DOI  :  10.1186/1471-2407-10-605

 received in 2010-05-21, accepted in 2010-11-04,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundHypoxia induces activation of the HIF-1 pathway and is an essential characteristic of malignant gliomas. Hypoxia has been linked to tumor progression, therapy resistance and poor prognosis. However, little is known about the impact of HIF-1α inhibition on radioresistance of malignant glioma.MethodsIn this study, we investigated the effects of the inhibition of HIF-1α on cell survival and radiosensitivity in U251MG and U343MG glioma cells, using two different strategies. HIF-1α inhibition was achieved by siRNA targeting of HIF-1α or via chetomin, a disruptor of interactions between HIF-1α and p300. The inhibition of the HIF-1 pathway was monitored by quantitative real-time PCR and Western blot analyses of the expression levels of HIF-1α and CA9. CA9 expression was investigated as a potential indicator of the efficacy of HIF-1 inhibition and the resulting radiosensitivity of malignant glioma cell lines was determined by clonogenic assay after irradiation under normoxic (2-10 Gy) or hypoxic (2-15 Gy) conditions.ResultsAlthough siRNA and chetomin show distinct modes of action, both attenuated the hypoxia-induced radioresistance of malignant glioma cell lines U251MG (DMF10: 1.35 and 1.18) and U343MG (DMF10: 1.78 and 1.48). However, siRNA and chetomin showed diverse effects on radiosensitivity under normoxic conditions in U251MG (DMF10: 0.86 and 1.35) and U343MG (DMF10: 1.33 and 1.02) cells.ConclusionsResults from this in vitro study suggest that inhibition of HIF-1α is a promising strategy to sensitize human malignant gliomas to radiotherapy and that CA9 could serve as an indicator of effective HIF-1-related radiosensitization.

【 授权许可】

CC BY   
© Kessler et al; licensee BioMed Central Ltd. 2010