肺腺癌靶向性超氧化物歧化酶的构建及功能分析
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浙江省自然科学基金资助项目(396007).


Construction and Functional Characterization of Lung Adenocarcinoma Targeting SOD
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This work was supported by a grant from The Zhejiang Natural Science Foundation of China (396007).

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    摘要:

    临床上,超氧化物歧化酶 (SOD) 的低肿瘤细胞定位能力限制了其在抗肿瘤领域的广泛应用,这一直是国内外学者们试图解决的难点. 研究中,以基因工程方法连接念珠藻Fe-SOD (iron-superoxide dismutase) 基因和抗SPC-A-1肺腺癌LC-1 ScFv (single chain Fv) 基因,并融合表达获得了SOD-ScFv融合蛋白. 纯化后SOD-ScFv表现出SOD和ScFv的双重活性. SPC-A-1肺腺癌细胞中,融合蛋白的异硫氰酸荧光素 (FITC) 染色追踪和自由基含量分析表明,SOD-ScFv具备识别SPC-A-1肺腺癌细胞、透膜并清除胞内自由基的功能,最终达到抑制肿瘤细胞生长的目的. 研究提出的靶向抗肿瘤机制将克服临床上SOD无目标趋向性和难于进入实体瘤的两大应用局限性,并提供了一种利用LC-1 ScFv来靶向投递抗肿瘤药物的思路.

    Abstract:

    In clinic, the low tumour-targeted ability of SOD is a critical shortage in its application, which is a difficulty for scientist at all time. For solving this problem, Nostoc commune CHEN iron-superoxide dismutase (Fe-SOD) and anti-lung adenocarcinoma LC-1 single chain Fv (ScFv) were fused, and the fusion protein named SOD-ScFv was expressed. After purification, fusion protein demonstrated both SOD and LC-1 antibody activities. The result of tracing of SOD-ScFv by FITC dyeing and quantification of ROS(reactive oxygan species) in SPC-A-1(lung adenocarcinoma) cells showed that the fusion protein possessed the ability to recognize SPC-A-1 cells and eliminate the cellular ROS. The tumour-targeted theory put up in this research will overcome two applied disadvantages of SOD in clinic: it neither target the tumour cell nor permeates through the cell membrane. Also, the research provides a feasible idea that ScFv can be used to target the anticancer drug to tumour.

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卢 敏,龚兴国,汪辰卉,郑 乐,郭建军,章申峰.肺腺癌靶向性超氧化物歧化酶的构建及功能分析[J].生物化学与生物物理进展,2006,33(1):51-58

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