全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
科技导报  2014 

重组F3肽-铜绿假单胞菌外毒素A抑制肿瘤生长

DOI: 10.3981/j.issn.1000-7857.2014.07.001, PP. 15-21

Keywords: F3,,铜绿假单胞菌外毒素A,受体,肿瘤

Full-Text   Cite this paper   Add to My Lib

Abstract:

为检测重组的F3肽-铜绿假单胞菌外毒素A(F3-PE39KDEL)的抗肿瘤作用,采用MTT法检测F3-PE39KDEL对人乳腺癌细胞MCF-7、人肺癌细胞A549、人卵巢癌细胞SKOV3和人肝癌细胞HepG2的生长抑制活性。采用半数致死剂量法观察F3-PE39KDEL对小鼠的毒性反应。以接种人肺癌细胞的裸鼠为模型,观察F3-PE39KDEL的抗肿瘤作用。结果显示,培养72、120h时,F3-PE39KDEL对于人肺癌细胞A549和人乳腺癌细胞MCF-7具有显著的抑制活性,IC50分别为0.41、0.42μg/mL,4.95、2.53μg/mL。毒性试验结果显示,静脉注射给予F3-PE39KDEL后小鼠的半数致死量为1.1782mg/kg,动物出现自发运动减少,死亡集中在给药后1d内,死亡动物及实验结束存活动物剖检未见异常。F3-PE39KDEL对荷瘤裸鼠具有较强的抗肿瘤活性,剂量分别为0.1、0.2、0.4mg/kg,其抑制率分别达到37.0%、43.2%、53.1%,显示出良好的量效关系。F3-PE39KDEL在靶向治疗肿瘤方面具有较好的应用前景。

References

[1]  Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease[J]. Nature Medicine, 1995, 1(1): 27-30.
[2]  吴学萍, 谢明均, 孙艳, 等. 短肽修饰的甲氨蝶呤的制备及细胞毒性作 用[J]. 中国医院药学杂志, 2011, 31(1): 32-35. Wu Xueping, Xie Mingjun, Sun Yan, et al. Preparation of methotrexate modified by small peptide and study on its cytotoxic effect[J]. Chinese Journal of Hospital Pharmacy, 2011, 31(1): 32-35.
[3]  周雅梅, 吴学萍, 曾理, 等. 肽修饰的的甲氨蝶呤体外抗肿瘤作用初步 研究[J]. 药学学报, 2012, 47(4): 452-458. Zhou Yamei, Wu Xueping, Zeng Li, et al. In vitro anti-tumor effect of methotrexate modified by peptide[J]. Acta Pharmaceutica Sinica, 2012, 47(4): 452-458.
[4]  Porkka K, Laakkonen P, Hoffman J A, et al. A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo[J]. Proceedings of the National Academy of Sciences, 2002, 99 (11): 7444-7449.
[5]  Grinstein E, Shan Y, Karawajew L, et al. Cell cycle- controlled interaction of nucleolin with the retinoblastoma protein and cancerous cell transformation[J]. Journal of Biological Chemistry, 2006, 281(31): 22223-22235.
[6]  Yates S P, Merrill A R. A catalytic loop within pseudomonas aeruginosa exotoxin A modulates its transferase activity[J]. Journal of Biological Chemistry, 2001, 276 (37): 35029-35036.
[7]  Yates S A S P, Merrill A R. Insight into the catalytic mechanism of pseudomonas aeruginosa exotoxin A[J]. Biochemistry, 2002, 277(48): 46669-46675.
[8]  祁志荣, 李虹. PE类重组免疫毒素的研究进展[J]. 微生物学免疫学进 展, 2006, 34(1): 50-53. Qi Zhirong, Li Hong. Advances in recombinant immunotoxin of PE class[J]. Progress in Microbiology and Immunology, 2006, 34(1): 50-53.
[9]  张艳, 刘秀群. 高效低毒的系列功能蛋白: 中国, 200410033621.6[P]. 2004-10-03. Zhang Yan, Liu Xiuqun. Series functional protein of high efficiency and low toxicity: CN, 200410033621.6[P]. 2004-10-03.
[10]  Taupiac M P, Bébien M, Alami M, et al. A deletion within the translocation domain of pseudomonas exotoxin A enhances translocation efficiency and cytotoxicity concomitantly [J]. Molecular Microbiology, 1999, 31(5): 1385-93.
[11]  Fitzgerald D J. Pastan I H. Recombinant pseudomonas exotoxin with increased activity: US, 5821238 A[P]. 1998-10-13.
[12]  朱海兵, 黄轶, 曾昭淳. F3重组毒素的克隆表达及纯化[J]. 科技导 报, 2009, 27(12): 19-22. Zhu Haibing, Huang Yi, Zeng Zhaochun. The cloning, expression and purification of F3 recombinant toxin [J]. Science & Technology Review, 2009, 27(12): 19-22.
[13]  刘新, 邵长伦, 孔雯, 等. 中药复方海藻制剂体外免疫调节、细胞毒和 抗氧化作用[J]. 中国海洋药物, 2009, 28(4): 13-16. Liu Xin, Shao Changlun, Kong Wen, et al. Immunomodulatory, cytotoxic and antioxidant effects of traditional Chinese medicine seaweed complex prescription in vitro[J]. Chinese Journal of Marine Drugs, 2009, 28(4): 13-16.
[14]  Thundimadathil J. Cancer treatment using peptides: Current therapies and future prospects [J]. Journal of Amino Acids, 2012, 2012: doi: 10.1155120121967347.
[15]  Winer I, Wang S, Lee Y E, et al. F3-targeted cisplatin-hydrogel nanoparticles as an effective therapeutic that targets both murine and human ovarian tumor endothelial cells in vivo [J]. Cancer Research, 2010, 70(21): 8674-83.
[16]  郭凯,赵晓燕,周红姿, 等. 重组人促性腺激素-铜绿假单胞菌外毒素 A蛋白的可溶性表达、纯化和对肿瘤细胞的抑制活性[J]. 山东科学, 2013, 26(2): 41-47. Guo Kai, Zhao Xiaoyan, Zhou Hongzi, et al. Soluble expression and purification of GnRH-PE39KDEL and the inhibition to the activity of a tumor cell [J]. Shandong Science, 2013, 26(2): 41-47.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133