重组免疫毒素抗c-Met/PE38KDEL对人大肠癌细胞株增殖及凋亡的影响  

Effects of recombinant immunotoxin anti-c-Met/PE38KDEL on the proliferation and apoptosis of human colorectal cancer cell lines

作　　者：徐伟[1] 朱晓娟[1] 蔡楠[1] 张秀华[1] 范志宁[1] 刘政[1] 季国忠[1] 

机构地区：[1]南京医科大学第二附属医院消化医学中心南京医科大学消化内镜研究所,南京医学硕士研究生210011

出　　处：《医学研究生学报》2011年第7期683-686,共4页Journal of Medical Postgraduates

基　　金：江苏省自然科学基金(BK2008483)

摘　　要：目的大肠癌是常见的恶性胃肠道肿瘤,近年来发病率有上升趋势。因此亟需探索新的治疗方法。文中观察重组免疫毒素(immunotoxin,IT)抗c-Met/PE38KDEL对大肠癌细胞的增殖抑制作用,为大肠癌的导向治疗奠定基础。方法分别用不同浓度IT处理大肠癌细胞系Colo205及SW480后,CCK-8试剂盒检测24、48 h细胞增殖抑制率;[3H]-亮氨酸掺入法测定IT对细胞5、24 h蛋白合成抑制的影响;caspase试剂盒检测细胞caspase-3、caspase-8活性变化。结果经不同浓度IT作用后,2株大肠癌细胞的增殖率及蛋白合成都有明显的降低,且呈时间和剂量依赖性,当IT浓度为10ng/ml与100ng/ml时,对2株细胞的增殖率及蛋白合成抑制作用较强(P<0.01);caspase活性测定显示,与对照组相比,IT浓度为100 ng/ml时2株细胞caspase-3与caspase-8都有显著增高。结论重组IT抗c-Met/PE 38KDEL对大肠癌细胞株有显著的增殖抑制及诱导凋亡的作用,为大肠癌的靶向治疗提供实验依据。Objective Colorectal cancer is a common gastroenteric malignancy,which has an increasing incidence in the recent years and therefore calls for the exploration of new treatment.Our study is to investigate the effect of recombinant immunotoxin(IT) anti-c-Met/PE38KDEL on the proliferation and apoptosis of human colorectal cancer cell lines.Methods Human colorectal cancer cell lines Colo205 and SW480 were treated with different concentrations of IT.The inhibition of the cell proliferation was determined by Cell Counting Kit-8 assay(CCK-8) at 24 and 48 hours,that of protein synthesis evaluated by -leucine incorporation assay at 5 and 24 hours,and the changes in the activity of caspase-3 and caspase-8 detected by designated caspase colorimetric protease assay.Results IT treatment significantly decreased the growth and protein synthesis of the colorectal cancer cells in a dose-and time-dependent manner,with more obvious effect at 10 and 100 ng/ml(P<0.01),and remarkably increased the activity of caspase-3 and caspase-8 at 100 ng/ml.Conclusion Recombinant IT anti-c-Met/PE38KDEL can inhibit the proliferation and induce the apoptosis of human colorectal cancer cell lines,which has offered some evidence for targeted therapies for colorectal cancer.

关 键 词：免疫毒素 大肠癌 凋亡 增殖 

分 类 号：R735[医药卫生—肿瘤]