文章摘要
王 芳,潘世扬,徐 婷,黄珮珺,徐 建,夏文颖,陆雅春,彭 蘡,秦雪君,耿 雁,孙瑞红,黄 蕾.抗人非小细胞肺癌单克隆抗体对肺腺癌抑制作用的实验研究[J].南京医科大学学报,2011,(7):940~944
抗人非小细胞肺癌单克隆抗体对肺腺癌抑制作用的实验研究
Experimental study on the inhibitory effect of monoclonal antibody against human non-small cell lung cancer on lung adenocarcinoma
投稿时间:2011-01-05  
DOI:10.7655
中文关键词: 非小细胞肺癌  单克隆抗体  凋亡  裸鼠
英文关键词: non-small cell lung cancer  monoclonal antibody  apoptosis  nude mice
基金项目:国家自然科学基金(30972821,30901344,30-901262);江苏省实验诊断学重点实验室基金(XK200731)
作者单位
王 芳 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
潘世扬 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
徐 婷 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
黄珮珺 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
徐 建 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
夏文颖 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
陆雅春 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
彭 蘡 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
秦雪君 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
耿 雁 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
孙瑞红 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
黄 蕾 南京医科大学第一附属医院医学检验科,江苏 南京 210029 
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中文摘要:
      目的:研究抗人非小细胞肺癌单克隆抗体(单抗)NJ488-1对肺腺癌的体内外抑制作用? 方法:将人肺腺癌细胞SPC-A1分别与不同浓度(0?200?400?800?1 600?2 000 μg/ml)的单抗NJ488-1在双层琼脂中共同培养2周,计算克隆形成率?抑制率;建立人肺癌移植瘤动物模型,腹腔注射不同剂量(200?400?800 μg)单抗或生理盐水,作为单抗组和对照组,测量肿瘤体积,3周后处死小鼠,称量肿瘤湿重,计算抑瘤率;400 μg/ml 单抗与SPC-A1细胞作用24?48 h后,观察细胞形态,流式细胞仪检测细胞凋亡率? 结果:软琼脂克隆形成试验中,200 μg/ml单抗作用SPC-A1细胞2周后克隆抑制率为23.4%,400 μg/ml达62.5%,800 μg /ml 及以上浓度抑制率达100%;裸鼠移植瘤实验,400?800 μg单抗组平均肿瘤体积显著小于对照组(P = 0.004,P = 0.003);4组小鼠平均瘤重组间差异有统计学意义(P = 0.044),其中400?800 μg单抗组平均瘤重显著低于对照组(P = 0.032,P = 0.015),200 μg 和800 μg单抗组间也存在显著差异(P = 0.048),200?400?800 μg单抗组抑瘤率分别为10.44%?37.29%和44.04%;400 μg/ml单抗作用于SPC-A1细胞24?48 h后,细胞逐渐出现凋亡改变,单抗组与对照组相比,总凋亡率显著增高(P 均 < 0.001),且呈现一定的时间依赖性?结论:单克隆抗体NJ488-1能抑制肺腺癌细胞SPC-A1在软琼脂上的克隆形成,并能抑制裸鼠体内移植瘤的生长,具有显著的抗肺腺癌活性,诱导细胞凋亡可能是其抑瘤功能发挥的机制之一?
英文摘要:
      Objective:To investigate the inhibitory effect of monoclonal antibody(McAb) NJ488-1 on the lung adenocarcinoma cell line SPC-A1 in vivo and in vivo. Methods:SPC-A1 cells were plated on a soft agar matrix and treated with McAb NJ488-1 (0, 200, 400, 800, 1600, 2000 μg/ml). After 2 weeks’ incubation, the colony formation efficiency and the inhibition ratio of colonies were calculated. Xenograft was established by subcutaneous injection of SPC-A1 cells and antibodies were administered intraperitoneally at three different doses (200, 400, 800 μg per mouse). Animals were monitored by tumor size. Three weeks after the initiation of treatment, tumors were removed and weighed, and tumor growth inhibition was calculated. SPC-A1 cells were cultured with or without 400 μg/ml McAb for 24 h or 48 h. The morphology changes of cells were observed and the apoptosis rates were measured by flow cytometry. Results:In soft agar assay, the colony formation efficiency in McAb groups reduced in a dose-dependent manner. The higher level of antibody inhibited colony formation compared to the lower one, with 62.5% inhibition ratio at 400 μg/ml vs 23.4% at 200 μg/ml. When the concentration of McAb was 800 μg/ml or even higher, the inhibition ratio was up to 100%. McAb caused varying degrees of decrease in tumor volume compared with control mice(P = 0.004, P = 0.003, 400 μg and 800 μg McAb group vs control). In the 200, 400, 800 μg McAb groups, tumor growth inhibition was 10.44%, 37.29% and 44.04%, respectively. The average tumor weights of the 400, 800 μg McAb group and the control group, the 200 μg McAb group and 800 μg McAb group were significantly different(P = 0.032, P = 0.015, P = 0.048, respectively). NJ488-1 led to the obvious cyto-morphology changes and significantly induced the apoptosis of SPC-A1 cells in a time-dependent manner(P < 0.001). Conclusion:The McAb NJ488-1 inhibited the growth of lung adenocarcinoma cell line both in vitro and in vitvo. It is suggested that cell apoptosis induced by NJ488-1 might be the mechanism of the anti-tumor activity.
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