Cellular Physiology and Biochemistry | |
Stabilisation and Knockdown of HIF - Two Distinct Ways Comparably Important in Radiotherapy | |
关键词: Stabiliser; Cancer; Radiotherapy; HIF; Hypoxia; | |
DOI : 10.1159/000335794 | |
学科分类:分子生物学,细胞生物学和基因 | |
来源: S Karger AG | |
【 摘 要 】
Background Radiotherapy is one of the most widely used treatments for cancer. The benefit of radiation is known to be negatively affected by tumor hypoxia and the expression of hypoxia-inducible factors (HIF), respectively. HIF-1α/ β and HIF-2α/ β are transcriptional activators of oxygen-regulated genes. The aim of the study was to examine cell type-specific effects of HIF-1α and -2α knockdown or oxygen-independent HIF-stabilisation on radiosensitivity. Methods Herein, we treated four different wildtype and HIF-1α- or HIF-2α-deficient human cancer cell lines, cultured under normoxic or hypoxic conditions, with ionising radiation in doses from 2 to 6 Gy and examined clonogenic survival. Furthermore, the cells were partly preincubated with a HIF-stabiliser (di-tert-butyroyl-oxymethyl-2,4-pyridine-dicarboxylate, tBu-2,4-PDC). Results The results show that both hypoxia exposure and treatment withtBu-2,4-PDC increased the radioresistance of human cancer cells. The HIF-mediated decrease of radioresponsiveness induced by the chemical stabiliser emerged to be as strong as the one caused by hypoxia. Clonogenic survival assays furthermore revealed that HIF-1 expression enhanced resistance to radiation, whereas knocking-down HIF-1 increased the sensitivity to radiation under normoxic as well as under hypoxic conditions. Conclusion These data extend previous observations of HIF-1α and broaden the view by showing HIF-2α inverse correlation between HIF expression and prognosis for the outcome of radiotherapy.
【 授权许可】
CC BY-NC-ND
【 预 览 】
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