Mohajeri Abbas, Sanaei Sarvin, Kiafar Farhad, Fattahi Amir, Khalili Majid, Zarghami Nosratollah
Department of Biotechnology, Zahravi Pharmaceutical Company, Tabriz, Iran.
Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2017 Apr;7(1):21-34. doi: 10.15171/apb.2017.004. Epub 2017 Apr 13.
Angiogenesis plays an essential role in rapid growing and metastasis of the tumors. Inhibition of angiogenesis is a putative strategy for cancer therapy. Endostatin (Es) is an attractive anti-angiogenesis protein with some clinical application challenges including; short half-life, instability in serum and requirement to high dosage. Therefore, production of recombinant endostatin (rEs) is necessary in large scale. The production of rEs is difficult because of its structural properties and is high-cost. Therefore, this review focused on the different expression systems that involved in rEs production including; mammalian, baculovirus, yeast, and Escherichia coli (E. coli) expression systems. The evaluating of the results of different expression systems declared that none of the mentioned systems can be considered to be generally superior to the other. Meanwhile with considering the advantages and disadvantage of E. coli expression system compared with other systems beside the molecular properties of Es, E. coli expression system can be a preferred expression system for expressing of the Es in large scale. Also, the molecular bioengineering and sustained release formulations that lead to improving of its stability and bioactivity will be discussed. Point mutation (P125A) of Es, addition of RGD moiety or an additional zinc biding site to N-terminal of Es , fusing of Es to anti-HER2 IgG or heavy-chain of IgG, and finally loading of the endostar by PLGA and PEG- PLGA nanoparticles and gold nano-shell particles are the effective bioengineering methods to overcome to clinical changes of endostatin.
血管生成在肿瘤的快速生长和转移中起着至关重要的作用。抑制血管生成是一种癌症治疗的假定策略。内皮抑素（Es）是一种有吸引力的抗血管生成蛋白，但存在一些临床应用挑战，包括半衰期短、在血清中不稳定以及需要高剂量。因此，大规模生产重组内皮抑素（rEs）是必要的。由于其结构特性，rEs的生产困难且成本高昂。因此，本综述聚焦于参与rEs生产的不同表达系统，包括哺乳动物、杆状病毒、酵母和大肠杆菌（E. coli）表达系统。对不同表达系统结果的评估表明，上述系统中没有一个能被认为普遍优于其他系统。同时，考虑到大肠杆菌表达系统与其他系统相比的优缺点以及Es的分子特性，大肠杆菌表达系统可能是大规模表达Es的首选表达系统。此外，还将讨论导致其稳定性和生物活性提高的分子生物工程和缓释制剂。Es的点突变（P125A）、在Es的N端添加RGD部分或额外的锌结合位点、将Es与抗HER2 IgG或IgG重链融合，以及最后用PLGA和PEG - PLGA纳米颗粒和金纳米壳颗粒负载恩度，都是克服内皮抑素临床变化的有效生物工程方法。
