[1]王楠,徐美兰,廖淑婷.AGGF1在结直肠癌细胞DNA损伤修复及化疗敏感性中的作用[J].南方医科大学学报,2018,(07):861.
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AGGF1在结直肠癌细胞DNA损伤修复及化疗敏感性中的作用()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2018年07期
页码:
861
栏目:
出版日期:
2018-06-30

文章信息/Info

Title:
Role of AGGF1 in DNA damage repair and modulating chemotherapy resistance in human colon cancer cells in vitro
作者:
王楠徐美兰廖淑婷
关键词:
AGGF1结直肠癌DNA双链断裂顺铂
Keywords:
AGGF1 colon cancer DNAdouble-strand breaks Cisplatin
摘要:
目的研究血管生成因子AGGF1在人结直肠癌细胞DNA损伤修复及化疗抵抗中的作用及机制。方法顺铂诱导结直肠 癌细胞株HCT116 细胞DNA损伤模型,运用siAGGF1 及siNC 转染结直肠癌细胞干扰AFFF1 的表达。Western blot 实验检测 AGGF1、γH2AX基因表达水平,免疫荧光法检测顺铂诱导HCT116细胞DNA损伤(双链断裂)后,γH2AX和AGGF1在损伤位点 的募集情况;MTS法检测损伤细胞的增殖情况;免疫组织化学方法检测结直肠癌及癌旁正常组织中AGGF1的表达水平。结果 Western blot结果显示顺铂处理HCT116细胞明显下调AGGF1表达,干扰AGGF1的表达抑制了γH2AX和NBS1;免疫荧光实 验表明AGGF1和γH2AX共定位,细胞增殖实验表明结直肠癌细胞对化疗的敏感性增加(P<0.01);AGGF1在结直肠癌组织中表 达高于相应癌旁组织(P<0.01),表明其可能与肿瘤的恶性表型相关。结论下调AGGF1基因可抑制结直肠癌细胞的DNA损伤 修复,提高其对化疗的敏感性,机制上可能与NBS1磷酸化相关。
Abstract:
Objective To investigate the role of AGGF1 in DNA damage repair and modulating chemotherapy resistance in human colon cancer cells. Methods Cisplatin-induced human colon cancer HCT116 cells transfected with AGGF1 siRNA and siNC via Lipofectamine 2000 were examined for AGGF1, γH2AX and pNBS1 expressions using Western blotting. Immunofluorescence analysis was used to detect the recruitment of phosphorylated γH2AX and AGGF1 at the site of cisplatin-induced double-strand DNA breaks, and MTS method was used to investigate the proliferation of the damaged cells. Immunohistochemical method was used to detect the expression level of AGGF1 in human colon cancer and adjacent normal tissues. Results Western blotting showed that AGGF1 expression was significantly down-regulated in HCT116 cells after cisplatin exposure, and transfection withAGGF1 siRNAobviously inhibited the expression of phosphorylated γH2AX and NBS1. Immunofluorescence assay showed the co-localization of AGGF1 and γH2AX. Down-regulation of AGGF1 mediated by siRNA obviously increased the chemosensitivity of the cells (P<0.01). In the clinical specimens, AGGF1 was found to be overexpressed in colon cancer tissues as compared with the adjacent normal tissues (P<0.01), suggesting its association with the malignant phenotype of the tumor. Conclusion Down-regulation of AGGF1 inhibits DNA damage repair and increases the chemosensitivity in colon cancer cells possibly in relation with the suppressed phosphorylation of NBS1.

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更新日期/Last Update: 1900-01-01