| LIU Jing-jia,WANG Jun-jie,ZHAO Yong,et al.Cetuximab affects the capicity of DNA repair in colorectal cancer cells after 125I seeds irradiation[J].Chinese Journal of Radiological Medicine and Protection,2012,32(6):578-582 |
| Cetuximab affects the capicity of DNA repair in colorectal cancer cells after 125I seeds irradiation |
| Received:May 02, 2012 |
| DOI：10.3760/cma.j.issn.0254-5098.2012.06.005 |
| KeyWords:C225 DNA damage repair Colorectal cancer cells Ku70 Akt |
| FundProject:国家自然科学基金面上项目(81071834) |
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| 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 groups: control group, 100 nmol/L C225 treatment group, 125I radioactive seeds continuous low-dose rate irradiation group and C225 combined with 125I radioactive seeds continuous low-dose 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. |
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