Radiosensitization by microRNA30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft*

Abstract

Abstract 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.