Please wait a minute...

中国生物工程杂志

China Biotechnology
China Biotechnology  2013, Vol. 33 Issue (4): 1-8    DOI:
    
Construction and Evaluation of the Mutated Anthrax Toxin Proteins as Drug Deliver System for Targeting Tumor Cells
LI Bing-juan1,2, LI Yu-xia1, LI Bei-ping1, LING Yan1, ZHOU Wei1, LI Wei-dong1, LIN Hai-long1, LIANG Long1, LIU Gang1, ZHANG Jin-hai2, CHEN Hui-peng1
1. Beijing Institute of Biotechnology, Beijing 100071, China;
2. Department of Life Science, ShenYang Pharmaceutical University, ShenYang 110016, China
Download: HTML   PDF(827KB) HTML
Export: BibTeX | EndNote (RIS)      

Abstract  Objective: The anthrax toxin proteins constitute a unique membrane translocation system which provide an attractive model system for the development of reagents for cell biology and therapeutics. The mutated anthrax toxin proteins PA and LF were constructed to target to tumor cells. Methods: The recombinant Rosseta(DE3) which harboring three kinds of mutated PA and LF were constructed separately. The cell viability after incubated with mutated PA and LF was detected by cytotoxicity assay. The ability of the mutated PA translocation system targeting to tumor cells was measured by the amount of the luciferase of intra-cellular. Results: The mutated PA can be cleaved by matrix metalloproteinases or uPA in vitro correctly. When the tumor cell incubated with the mutated PA and LF,the cell viability was decreased remarkably. The amount of the luciferase of intra-cellular can correctly reflex the ability of the mutated PA translocation system targeting to tumor cells. Conclusions: These mutated PA proteins showed natural biological activities and had the ability of targeting to tumor cells. These results provide a new insight for the study of the antitumor drugs.

Key wordsAnthrax toxin      Protective antigen      Luciferase      Matrix metalloproteinases      Targeting tumor therapy     
Received: 14 August 2012      Published: 25 April 2013
ZTFLH:  Q819  
Cite this article:

LI Bing-juan, LI Yu-xia, LI Bei-ping, LING Yan, ZHOU Wei, LI Wei-dong, LIN Hai-long, LIANG Long, LIU Gang, ZHANG Jin-hai, CHEN Hui-peng. Construction and Evaluation of the Mutated Anthrax Toxin Proteins as Drug Deliver System for Targeting Tumor Cells. China Biotechnology, 2013, 33(4): 1-8.

URL:

https://manu60.magtech.com.cn/biotech/     OR     https://manu60.magtech.com.cn/biotech/Y2013/V33/I4/1

[1] Liu S, Bugge T H, Leppla S H, Targeting of tumor cells by cell surface urokinase plasminogen activator-dependent anthrax toxin. J Biol Chem, 2001,276(21):17976-17984.
[2] Mendes O, Kim H T, Stoica G. Expression of MMP2, MMP9 and MMP3 in breast cancer brain metastasis in a rat model. Clin Exp Metastasis, 2005,22(3): 237-246.
[3] Kim H J, Park C, Jung W H, et al. Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ and invasive ductal carcinoma of the breast. Yonsei Med, 2006,47(3):333-342.
[4] Wiercinska E, Naber H, Pardali E, et al. The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system. Breast Cancer Res Treat, 2011,(128):657-666.
[5] Kai Kessenbrock, Vicki Plaks, Zena Werb. Matrix metalloproteinases: regulators of the tumor microenvironment.Cell, 2010,4(141):52-67.
[6] Mekkawy A H, David L Morris, Pourgholam M H.Urokinase plasminogen activator system as a potential target for cancer therapy. Future Oncol,2009,5(9):1478-1499.
[7] Carlo Petosa, John Coller R, Kurt R Klimpel, et al.Crystal structure of the anthrax toxin protective antigen.Nature, 1997,2(385):833-838.
[8] Roopali Roy, Jiang Yang, Marsha A Moses. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. Journal of Clinical Oncology,2009,11(27):5287-5297.
[9] Liu S, Wang H, Brooke M Currie. Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature. The Journal of Biological Chemistry, 2008, 1( 283):529-540.
[10] Jeffrey M Schafer, Diane E Peters, Thomas Morley. Efficient targeting of head and neck squamous cell carcinoma by systemic administration of a dual uPA and MMP-activated engineered anthrax toxin. PLoS ONE,2011,5(6):1-9.
[11] Randall W Alfano, Stephen H Leppla, Shihui Liu, et al. Inhibition of tumor angiogenesis by the matrix metalloproteinaseactivated anthrax lethal toxin in an orthotopic model of anaplastic thyroid carcinoma. Mol Cancer Ther, 2010,9(1): 190-201.
[12] Cunningham K, Lacy D B, Mogridge J, et al. Mapping the lethal factor and edema factor binding sites on oligomeric anthrax protective antigen. Proc Natl Acad Sci USA, 2002,99(10): 7049-7053.
[13] Chvyrkova I, Zhang X C, Terzyan S. Lethal factor of anthrax toxin binds monomeric form of protective antigen. Biochem Biophys Res Commun, 2007,360(3): 690-695.
[14] Abrami L, Reig N, van der Goot F G, Anthrax toxin: the long and winding road that leads to the kill. Trends Microbiol, 2005,13(2): 72-78.
[1] ZHAO Yuan-bo, HONGDu Bei-qi, CHEN Ying-yu. Establishment of p62/SQSTM1-luciferase Based Method for Cellular Autophagic Flux Determination[J]. China Biotechnology, 2016, 36(1): 55-62.
[2] YE Yu-chen, ZHAO Jun-long, WANG Lin, DUAN Juan-li, GAO Chun-chen, QIN Hong-yan, DOU Ke-feng. Construction of A Cell Line EGFP-Luc-Hepa1-6 and Its Application in the Mouse Model of the Hepatoma[J]. China Biotechnology, 2015, 35(5): 1-7.
[3] LI Hong-yi, XI Qian-yun, ZHANG Yong-liang. Identification miRNAs That Regulate Porcine TNF-α Expression Through Targeting TNF-α UTR[J]. China Biotechnology, 2014, 34(10): 35-40.
[4] FAN Li-xia, GAO An-hui, ZHOU Yu-bo, LI Jia. Establishment of a Cell-based High-throughput Screening Model Targeting the IRE1/XBP1 Signaling Pathway[J]. China Biotechnology, 2012, 32(01): 73-80.
[5] DONG Lei, ZHANG Xiao-peng, YI Shao-qiong, MAO Ya-li, YU Ting, HOU Li-hua, FU Ling, YU Chang-ming, CHEN Wei. In vivo Bioluminescence Imaging of Luc Labeled Human PSCA-expressed Tumor in Mouse Model[J]. China Biotechnology, 2011, 31(02): 1-6.
[6] . Immobilization of Luciferase by Cloning and Expression of Biotinylated Luciferase[J]. China Biotechnology, 2007, 27(9): 41-46.
[7] . Construction and expression in vitro of RU486-inducible regulatory vector[J]. China Biotechnology, 2007, 27(6): 1-5.
[8] . The SARS-CoV 3a and 7a protein may enhance the induction of IFN-β[J]. China Biotechnology, 2006, 26(12): 6-10.