Objective To investigate the effect and mechanism of osthol(OST)on radiosensitization of 4T1 cells.Methods 4T1 cells were treated with different concentrations of OST(25,50,75,100,125,150,175,200 μmol/L)for 24 h,and then the cell viability was detected by CCK-8.4T1 cells were divided into IR group and OST(50 µmol/L)+IR group,and then clone plate formation assay was used to detect the effect of radiotherapy sensitization.4T1 cells were divided into control group,OST(50 μmol/L)group,IR(2 Gy)group,OST(50 μmol/L)+IR(2 Gy)group.TUNEL staining was used to detect the apoptosis,and Western blot was used to detect Nrf2 and NQO1 protein expression levels in 4T1 cells.Results Compared with 0 μmol/L OST group,the prolife-ration activity of 4T1 cells was significantly decreased in different OST groups(25,50,75,100,125,150,175,200 μmol/L)(P<0.05).Compared with IR group,the cell clonal survival fraction in OST+IR group was significantly decreased(P<0.05).Compared with IR group,the sensitization ratio of cells in OST+IR group was 1.14.Compared with control group,the apoptosis rate was increased in OST group and IR group(P<0.05).Compared with IR group,the apoptosis rate was significantly increased in OST+IR group(P<0.05).Compared with control group,the protein expression levels of Nrf2 and NQO1 were significantly increased in OST group(P<0.05),while the protein expression levels of Nrf2 and NQO1 was significantly decreased in IR group(P<0.05).Compared with IR group,the expressions of Nrf2 and NQO1 were significantly decreased in OST+IR group(P<0.05).Conclusion Osthol can increase the radiosensitivity of breast cancer cells via the Nrf2/NQO1 pathway.
关键词
乳腺癌/蛇床子素/放疗增敏/4T1细胞/Nrf2/NQO1通路
Key words
breast cancer/osthol/radiosensitivity/4T1 cells/Nrf2/NQO1 pathway