新型截短肠毒素C2突变株抑制肿瘤细胞生长(英文)  

Inhibiting tumor-cell growth by novel truncated staphylococcal enterotoxin C2 mutant

作　　者：回晶[1,2] 肖芳[1] 李辉[1] 崔小进[1] 刘宏生[1] 胡风庆[1] 

机构地区：[1]辽宁大学生命科学院生物材料和生物制药实验室,沈阳110036 [2]沈阳药科大学制药工程学院,沈阳110016

出　　处：《生物工程学报》2011年第6期891-899,共9页Chinese Journal of Biotechnology

基　　金：辽宁省教育厅高等学校科研基金(Nos.L2010150,2008223,05L148);沈阳发改委高技术研发基金(No.2010-16);辽宁省博士后基金(No.2008189);辽宁大学青年科研基金(No.2008LDQN25)资助~~

摘　　要：在恶性肿瘤的治疗中,肠毒素C2(SEC2)的临床应用由于其副作用而被严重限制。利用SEC2基因截短技术,获得保留T细胞刺激活力又不引发催吐效应的SEC2突变株,可有效解决这个问题。根据噻唑蓝比色法(MTT)分析结果,新型截短肠毒素C2突变株(NSM)可显著刺激T细胞增殖,并且可显著抑制人大肠癌细胞(CX-1)和人乳腺癌细胞(MCF-7)生长。NSM的T细胞刺激能力和抑瘤效果与SEC2相似。动物研究结果证明NSM不再引发呕吐效应,且可显著抑制荷瘤小鼠的肿瘤生长。因此,这种可抑制肿瘤细胞生长的新型截短肠毒素C2突变株有可能成为无副作用的新型抗肿瘤生物制剂。Clinical application of staphylococcal enterotoxin C2（SEC2） was restricted during the cure of malignant tumor due to its side-effects.The aim of this study was to obtain SEC2 mutant,preserving the important functional sites responsible for the T-cell stimulatory activities but removing the sites responsible for emetic activity,through truncation of SEC2.It would efficiently solve the question of SEC2 side-effect.According to the results of methyl thiazol tetrazolium（MTT） assay in vitro,novel truncated SEC2 mutant（NSM） efficiently stimulated T-cell proliferation and inhibited the growth of such tumor cells as human colorectal cancer cells（Cx-1） and human breast cancer cells（MCF-7） in vitro.Activities of T cell stimulating and anti-tumor of NSM were similar to those of SEC2.According to results of animal experiments,the mutant no longer induced emetic response even if the dose was a 10-fold excess of the amount of SEC2 required.And also,NSM obviously inhibited the tumor growth in tumor-bearing mice.Therefore,we obtained novel truncated staphylococcal enterotoxin C2 mutant,which could efficiently inhibit the growth of tumor cells.It will become novel anti-tumor agents with the lowest side-effects and best treatment effects in clinic.

关 键 词：肠毒素 抗肿瘤 超抗原 外周血单核细胞增殖 

分 类 号：R73-3[医药卫生—肿瘤]