Study Of Radiosensitivity And Underlying Mechanisms Of Cordycepin On Breast Cancer Cells

Radiation therapy toward malignancies is often ineffective owing to radioresistance of cancer cells.On the basis of anti-tumor properties of cordycepin,we examined the effects of cordycepin on sensitizing breast cancer cells toward radiotherapy.MTT and clonogenic survival assays showed that cordycepin treatment restrained the proliferation of MCF-7 and MDA-MB-231 human breast carcinoma cells following irradiation.To uncover the underlying mechanism,flow cytometry analysis was performed and revealed that cordycepin administration promoted apoptosis of MCF-7 and MDA-MB-231 cells following irradiation.The breast cancer cells cultured with cordycepin harbored higher levels of intracellular reactive oxygen species(ROS)and incremental numbers of y-H2AX foci after irradiation exposure.Importantly,cordycepin treatment down-regulated the expression levels of Nuclear factor erythroid 2-related factor(Nrf2)and a series of downstream genes,such as heme oxygenase-1(HO-1),to fight against ROS in breast cancer cells exposed to irradiation.Tumor xenograft study using nude mice exhibited that pre-cultured with cordycepin inhibited the proliferation of breast cancer cells after irradiation in vivo.Together,our observations demonstrate that cordycepin treatment sensitizes breast carcinoma cells toward irradiation via Nrf2/HO-1/ROS axis.Thus,our findings provide novel insights into the function and the underlying mechanism of cordycepin in radiation therapy,and suggest that cordycepin might be employed as a radiosensitizer during radiotherapy toward breast cancer in a pre-clinical setting.Objective To explore the radioprotective effect of 3,3-diindolylmethane(DIM)on y-radiation-induced injury in hematopoietic system and the involved mechanisms.Methods:Thirty C57BL/6 mice were randomly divided into three groups,1)control group,2)irradiated group,3)DIM + irradiation group(n=10 for each).Irradiated group and DIM + irradiation group accepted 2 Gy total body irradiation,dose rate 1.0 Gy/min.Mice in DIM + irradiation group were intraperitoneally injected DIM(75 mg/kg)30 min before irradiation.Control group and irradiated group were treated with control solution.Mice were sacrificed 7 days and 15 days after irradiation.Peripheral blood was taken to determine blood counts.Bone marrow cells were taken to determine the number of nucleated cells,intracellular reactive oxygen species(ROS)level,and colony formation ability.Results Compared with the control group,the number of WBC,PLT,BMNCs and CFU-GM were significantly reduced in irradiated mice.The ROS level of bone marrow cells was significantly increased(P<0.05).Moreover,compared with 15 d,the injury effects of irradiation of 7 d was more serious.However,Intraperitoneal injection of DIM significantly reduced the injury effects of irradiation in mice(P<0.05).Conclusions DIM has a protective effect on hematopoietic damage after 2 Gy irradiation in mice,and its effect may be related with reducing the level of ROS.