| 刘敬佳,王俊杰,赵勇,等.西妥昔单抗对125I粒子照射结直肠癌细胞DNA修复能力和信号传导通路的影响[J].中华放射医学与防护杂志,2012,32(6):578-582.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].Chin J Radiol Med Prot,2012,32(6):578-582 |
| 西妥昔单抗对125I粒子照射结直肠癌细胞DNA修复能力和信号传导通路的影响 |
| Cetuximab affects the capicity of DNA repair in colorectal cancer cells after 125I seeds irradiation |
| 投稿时间：2012-05-02 |
| DOI：10.3760/cma.j.issn.0254-5098.2012.06.005 |
| 中文关键词: 西妥昔单抗 DNA损伤修复 结直肠癌细胞 Ku70 Akt |
| 英文关键词:C225 DNA damage repair Colorectal cancer cells Ku70 Akt |
| 基金项目:国家自然科学基金面上项目(81071834) |
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| 中文摘要: |
| 目的 探讨西妥昔单抗(C225)对125I 粒子照射下结直肠癌CL187细胞DNA损伤修复和信号传导通路的影响。方法 实验分为空白对照组,100 nmol/L C225处理组,单独125I粒子持续低剂量率照射组和C225联合125I粒子持续低剂量率照射组。在吸收剂量达4 Gy后48 h,经细胞免疫荧光检测各组细胞中γH2AX聚集点数量以及γH2AX聚集点阳性细胞比例。提取细胞内总蛋白,Western blot检测DNA修复蛋白的变化。在吸收剂量达4 Gy后即刻提取总蛋白,Western blot分析在照射过程中C225对EGFR下游信号通路中蛋白分子的影响。结果 与单独125I粒子持续低剂量率照射组细胞相比,C225联合125I持续低剂量率照射组细胞内残余的γH2AX聚集点数量和γH2AX聚集点阳性的细胞比例均高(t=8.0和6.8,P<0.05),并且细胞中DNA修复蛋白Ku70和DNA-PKcs的含量偏低(t=6.6和5.7,P<0.05)。Western blot结果显示,在125I粒子持续低剂量率照射过程中,C225能够降低细胞内EGFR的水平(t=4.9,P<0.05),抑制Akt的活化(t=5.5,P<0.05)。结论 在125I放射性粒子持续低剂量率照射下,C225可以降低细胞内Ku70和DNA-PKcs的含量,并抑制Akt活化,减弱CL187细胞的DNA损伤修复能力。 |
| 英文摘要: |
| 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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