新型截短肠毒素C2突变株抑制肿瘤细胞生长
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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。


Inhibiting tumor-cell growth by novel truncated staphylococcal enterotoxin C2 mutant
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Higher Education Department of Liaoning Province Research Fund (Nos. L2010150, 2008223, 05L148), High-Tech R&D Projects in Shenyang Development and Reform Commission (No. 2010-16), Liaoning Province Post-doctoral Fund of China (No. 2008189), Youth Science

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    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

    Abstract:

    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.

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回晶,肖芳,李辉,崔小进,刘宏生,胡风庆. 新型截短肠毒素C2突变株抑制肿瘤细胞生长[J]. 生物工程学报, 2011, 27(6): 891-899

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  • 收稿日期:2010-07-18
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