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NK细胞联合西妥昔单抗对大肠癌细胞ADCC作用的研究
The ADCC Function of NK Cells Combined with Cetuximab on Colon Cancer Cells
【摘要】 目的比较3株肠癌细胞株(LOVO、SW480、SW620)与自然杀伤(natural killer,NK)细胞、西妥昔单抗(Cetuximab)混合作用之后,NK细胞抗体依赖的细胞介导的细胞毒作用(antibody dependent cell cytotoxicity,ADCC),探讨Cetuximab抗肿瘤过程中ADCC的作用。方法免疫组织化学方法检测3种不同肠癌细胞系(LOVO、SW480、SW620)的EGFR表达水平;MTT法检测6种不同浓度Cetuximab作用48h后肿瘤细胞的生长抑制情况;NK细胞与Cetuximab包被的肿瘤细胞共孵育,LDH法检测NK细胞的ADCC功能变化。结果免疫组织化学结果显示,3株细胞EGFR表达:LOVO(),SW480(+),SW620(-);Cetuximab对LOVO细胞和SW480细胞的生长抑制呈剂量依赖,对SW620细胞无抑制作用;LOVO细胞和SW480细胞经Cetuximab处理后,NK细胞的ADCC作用均增强且有统计学意义(P<0.05)。结论单独的Cetuximab可抑制EGFR阳性的LOVO细胞和SW480细胞,而对EGFR阴性的SW620细胞生长抑制作用不明显,所选的2株EGFR阳性肿瘤细胞都可被Cetuximab所介导ADCC作用所抑制,高EGFR表达的肿瘤细胞更加敏感。
【Abstract】 Objective To compare the ADCC activity of natural killer(NK)cells induced by Cetuximab on three colon cancer cell lines(LOVO,SW480,SW620).Methods Immunohistochemistry assay was applied to detect EGFR expression in colorectal cancer cell lines(LOVO,SW480,SW620);then six different concentrations of Cetuximab was applied to these tumor cells,the inhibition on cell proliferation was determined by MTT assay after 48 hours;Human NK cells stimulated with Cetuximab-coated tumor cells were assessed for ADCC activity by LDH assay.Results Immunohistochemistry results showed different EGFR expression levels in these colon cancer cell lines: LOVO(■),SW480(+),SW620(-);Cetuximab inhibited the proliferation of LOVO cells and SW480 cells in a dose-dependent manner and showed almost no inhibitory effect on SW620 cells;the ADCC activity of NK cells on both LOVO cells and SW480 cells was enhanced.Conclusion Cetuximab alone can restrain the growth of EGFR positive LOVO and SW480 cells and its inhibitory effect on SW620 cells is weak;The ADCC activity of NK cells plays an important role in Cetuximab induced anti-EGFR positive colon cancer cells reaction,and a stronger ADCC activity is associated with a higher EGFR expression level in tumor cells.
【Key words】 antibodies,monoclonal; antibody-dependent cell cytotoxicity; killer cells,natural; receptor,epidermal growth factor;
- 【文献出处】 福建医科大学学报 ,Journal of Fujian Medical University , 编辑部邮箱 ,2012年01期
- 【分类号】R392.11
- 【被引频次】3
- 【下载频次】372