~125I Seeds Irradiation To Influence HIF-1α Expression And Induce Apoptosis Of Human Breast Cancer Cell Line (MCF-7) In Vitro

Objective:To study the effect of low dose rate and continuous irradiation with ¹²⁵I seeds in influence HIF-1αexpression,inhibit tumor cell growth and induce apoptosis, to explore the mechanism of irradiation damage in human breast cancer cell line in vitro.Methods:The irradiator consisted of nine Model 6711 ¹²⁵I seeds,each with 29.60MBq of apparent activity.Eight seeds were equally spaced around the circumference of a 3-cm diameter circle and the ninth seed was confined to the center. MCF-7 cells were placed 5mm above the seed plane and delivered dose of 100cGy, 200cGy,300cGy(at initial dose rate of 4.866 cGy/h).Expressions of Hypoxia inducible factor-la genes was detected by RT-PCR and Western blotting,respectively. Cytometry analyzed cell growth condition.The rate of apoptosis was determined by flow cytometry.Transmission electron microscope observe MCF-7 cells apoptosis condition of subcellsular level.Results:After being irradiated with 100cGy,200cGy, 300cGy,the HIF-1αmRNA expression of the MCF-7 cells determined by RT-PCR was down-regulated dramatically.The results of the experiment group was significant difference compared with that of the control group(P＜0.01).Western blotting analyses of this proteins showed similar expression pattern to that determined with RT-PCR,There was significant difference between the two groups(P＜0.01).Cell growth velocity was determined by Cytometry,that of the experiment group was step down dramatically.It has significant difference compared with the controls(P＜0.01). Flow cytometry showed that the apoptosis rates of the experiment group was down-regulated dramatically(P＜0.01).Transmission electron microscope observe obvious MCF-7 cell apoptosis in the dose of 200cGy,300cGy of the experiment group,respectively.Conclusions:Continuous irradiation of low dose rate by ¹²⁵I seeds for 100cGy,200cGy,300cGy(≤4.866 cGy/h)promote the apoptosis and decrease the expression of HIF-1αof MCF-7 cell in the experiment group significantly.The results demonstrated that low dose rate and continuous ¹²⁵I seed irradiation is effective on reducing the expression of HIF-1α,inhibiting cell growth and inducing the damage of MCF-7 cell.