Question: 

Radiotherapy is one of the most widely used treatments of cancer. The outcome of radiation is known to be negatively affected by tumor hypoxia and the expression of the hypoxia-inducible factor HIF-1, respectively. The aim of this study was to investigate if either diminishing HIF protein by RNAi treatment or chemical stabilisation of HIF could impair radioresponsiveness of tumor cells in vitro.

Methodology: 

Several cell lines originated from different human tissues were either transfected with siRNA to inhibit HIF-a expression or were pretreated with a new self synthesised HIF-stabilizer (PDC). Cells were cultured under well defined oxygen concentrations and effects of ionizing radiation with doses up to 4 Gy were investigated by clonogenic survival assays. Impact on HIF protein levels were estimated by immunoblotting.

Result: 

Clonogenic survival assay revealed HIF-1 expression could enhance the resistance to radiation, whereas knocking down HIF-1 could increase the sensitivity to radiation. The present study demonstrated that hypoxia mimetic PDC could increase the radioresistance of several human cancer cells. HIF-mediated decrease of radioresponsiveness induced by the chemical stabilizer emerged to be as strong as by hypoxia.

Conclusion: 

This data is consistent with the observed inverse correlation between HIF-1a tumor expression and prognosis for the outcome of radiotherapy. HIF-1a inhibiting agents are promising tools to improve radiotherapy of hypoxic tumors. The use of HIF stabilizers as PDC is potentially indicated to physiologically stimulate the endogenous erythropoietin production of anemic patients.