Objective We aimed to observe the radiosensitization effect of mir-30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft and to explore the underlying mechanism.Methods A549 cell lines with either stabl...Objective We aimed to observe the radiosensitization effect of mir-30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft and to explore the underlying mechanism.Methods A549 cell lines with either stable upregulation or downregulation of mir-30a-5p,and their negative control,were transfected with lentivirus vectors.These cell lines were used to establish a nude mouse model with subcutaneous lung-cancer xenograft.Each group was randomly divided into irradiated and non-irradiated groups.The radiosensitization effect of mir-30a-5p in vivo was studied by observing xenograft growth trends and tumor weight.The mechanisms involved in this radiosensitization were investigated by detecting expressed radiosensitization-related proteins,using immunohistochemistry and Western blotting.Results The expression level of mir-30a-5p in the lenti-mir-30a-5p group was higher than that in the negative control(lenti-GFP)group and lower in the lenti-inhibitor group(P<0.05).Subcutaneous lung-cancer xenografts in the irradiation group and lenti-mir-30a-5p increased in size slowly;tumors were lighter and tumor inhibition rates were higher than those in the non-irradiation and lenti-GFP groups.In contrast,the opposite of these effects was observed in the lenti-inhibitor group.Immunohistochemistry and Western blotting indicated that ATM protein expression level was lower in the lenti-mir-30a-5p group,with or without irradiation,compared to that in the lenti-GFP group.ATM protein levels were higher in the lenti-inhibitor groups.The phosphorylation level of ATM at residue 1981 was low in the groups without irradiation and increased significantly after irradiation(P<0.05).Moreover,the phosphorylation level was lower in the lenti-mir-30a-5p group and higher in the lenti-inhibitor group than that in the lenti-GFP group after irradiation(P<0.05).Conclusion Mir-30a-5p enhanced the radiosensitivity of nude mice with subcutaneous lung-cancer xenografts by inhibiting ATM phosphorylation.展开更多
基金supported by the National Science Fund Project (No. 81872471)the National Natural Science Foundation of China and the Science Foundation of the Second Affiliated Hospital of Xi’an Jiaotong University (No. YJ(QN)202025)
文摘Objective We aimed to observe the radiosensitization effect of mir-30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft and to explore the underlying mechanism.Methods A549 cell lines with either stable upregulation or downregulation of mir-30a-5p,and their negative control,were transfected with lentivirus vectors.These cell lines were used to establish a nude mouse model with subcutaneous lung-cancer xenograft.Each group was randomly divided into irradiated and non-irradiated groups.The radiosensitization effect of mir-30a-5p in vivo was studied by observing xenograft growth trends and tumor weight.The mechanisms involved in this radiosensitization were investigated by detecting expressed radiosensitization-related proteins,using immunohistochemistry and Western blotting.Results The expression level of mir-30a-5p in the lenti-mir-30a-5p group was higher than that in the negative control(lenti-GFP)group and lower in the lenti-inhibitor group(P<0.05).Subcutaneous lung-cancer xenografts in the irradiation group and lenti-mir-30a-5p increased in size slowly;tumors were lighter and tumor inhibition rates were higher than those in the non-irradiation and lenti-GFP groups.In contrast,the opposite of these effects was observed in the lenti-inhibitor group.Immunohistochemistry and Western blotting indicated that ATM protein expression level was lower in the lenti-mir-30a-5p group,with or without irradiation,compared to that in the lenti-GFP group.ATM protein levels were higher in the lenti-inhibitor groups.The phosphorylation level of ATM at residue 1981 was low in the groups without irradiation and increased significantly after irradiation(P<0.05).Moreover,the phosphorylation level was lower in the lenti-mir-30a-5p group and higher in the lenti-inhibitor group than that in the lenti-GFP group after irradiation(P<0.05).Conclusion Mir-30a-5p enhanced the radiosensitivity of nude mice with subcutaneous lung-cancer xenografts by inhibiting ATM phosphorylation.
