Hypoxia-Inducible Factor-1α Protects Cervical Carcinoma Cells from Apoptosis Induced by Radiation via Modulation of Vascular Endothelial Growth Factor and p53 under Hypoxia
Zhichao Fu, Dongsheng Chen, Huihua Cheng, Fengmei Wang
Department of Radiology, Fuzhou General Hospital, Fuzhou, Fujian, China (mainland)
Med Sci Monit 2015; 21:318-325
The aim of the study was to assess the role of irradiation in the expression of HIF-1a, VEGF, and P53 in human cervical carcinoma cells under a simulated hypoxia environment.
Material and Methods: The tetrazolium-based colorimetric cellular assay (MTT) and flow cytometry (FCM) were used to detect the growth inhibition rates of HeLa cells in different groups. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to observe gene and protein expression of HIF-1α, VEGF, and P53. The effect of HIF-1α on radioresistance and expression of VEGF and P53 were confirmed with the HIF-1α siRNA in vivo and in vitro.
Results: Hypoxic conditions enhanced the radiation resistance dependent on HIF-1α by elevating the expression of VEGF and inhibiting the expression of p53. After transfection of HIF-1α siRNA, MTT assay showed the survival rates were increased in the cells receiving irradiation under hypoxia. The expression of VEGF decreased significantly more than that of cells transfected with sense oligodeoxynucleotides, while an opposite result was found in the expression of P53 protein in the same X-ray dose (p<0.05). In vivo, the radioresistance of HIF-1α was consistent with the results in vitro.
Conclusions: In the future, we might inhibit human cervical cancer progression and enhance the radiosensitivity by inhibiting HIF-1α to reduce VEGF and increase P53 expression. The challenge is how to use this information to optimize cancer therapy.
Keywords: Apoptosis, Anoxia, Animals, Carcinoma - metabolism, Disease Progression, Flow Cytometry, Hela Cells, Hypoxia-Inducible Factor 1, alpha Subunit - metabolism, Mice, Mice, Inbred BALB C, Oligonucleotides - chemistry, RNA, Small Interfering - metabolism, Tumor Suppressor Protein p53 - metabolism, Uterine Cervical Neoplasms - metabolism, Vascular Endothelial Growth Factor A - metabolism, X-Rays