Cetuximab affects the capicity of DNA repair in colorectal cancer cells after 125Ⅰ seeds irradiation / 中华放射医学与防护杂志

ABSTRACT

Objective To investigate the effect of C225 on DNA repair and molecular pathways in CL187 colorectal cancer cells after irradiated by 125Ⅰ radioactive seeds.Methods In the experiment involved were four groupscontrol group,100 nmol/L C225 treatment group,125Ⅰ radioactive seeds continuous low-dose rate irradiation group and C225 combined with 125Ⅰ radioactive seeds continuous lowdose rate irradiation group.Cells were collected at 48 h after 4 Gy irradiation,and γH2AX foci/cell and γH2AX foci positive cells were counted with immunofluorescence.At the same time,DNA repair proteins were detected by Western blot.Cells were lyzed immediately after 4 Gy irradiation,and changs in EGFR downstream signaling molecules were detected by Western blot.Results Compared with 125Ⅰ seeds irradiated cells,cells treated with C225 and 125Ⅰ seeds irradiation showed more γH2AX foci per cell (t =8.0,P =0.05),and more γH2AX foci positive cells (t =6.8,P ＜ 0.05) and less expression of Ku70 (t =6.6,P ＜ 0.05) and DNA-PKcs (t =5.6,P ＜ 0.05).Combined with 125Ⅰ-CLDR irradiation,C225 reduced cellular EGFR level(t =4.9,P ＜0.05) and inhibited the activation of Akt(t =5.5,P ＜0.05).Conclusions In the condition of 125Ⅰ seeds irradiation,C225 reduced the expression of Ku70 and DNA-PKcs,inhibited the activation of Akt and attenuated the DNA damage repair capacity in CL187 colorectal cancer cells.