血管紧张素1-7改构体对A549细胞生长的抑制作用

目的:以D型氨基酸替代的方式和C端及N端改构的方式构建2种能够抵抗蛋白酶降解的血管紧张素Ang1-7异构体小肽血管紧张素改构体1和2,对其抗肿瘤细胞系A549活性进行初步研究,以期为长效型Ang1-7改构类抗肿瘤药的应用提供理论依据。方法:HPLC法检测2种改构体抗酶降解的能力;用带荧光标记的Ang1-7对A549细胞进行药物亲和实验,并用无标记的药物拮抗这种配体亲和;用MTT法检测Ang1-7及2种改构体对A549细胞增殖的影响。结果:2种改构体均能抗血管紧张素转化酶、中性内肽酶、亮氨酸内肽酶的降解;带荧光标记的Ang1-7能够和A549细胞结合,且这种结合可以被无标记的2种改构体竞争性拮抗;Ang1-7和2种改构体能抑制A549细胞增殖。结论:构建了能够抵抗酶降解,在体外能结合于A549细胞表面并抑制A549细胞增殖的2种Ang1-7改构体小肽,为该小肽进一步的体内抗癌研究及应用奠定了基础。

Inhibition Effect of Angiotensin 1-7 Mimic Peptides on A549 Cell

Objective: Two kinds of angiotensin Ang1-7 mimic peptides named angiotensin mimic peptide 1 and 2 were synthesized by the method of D-amino acid substitution and N-and C-terminus modification in order that they can resist protease degradation.Then A549 cell line was used to investigate the anti-tumor effect of mimic peptides.We expect the present study will shine light on the development and application of long-acting Ang1-7-associated anti-cancer drugs.Methods: HPLC was used to detect the degradation resistant ability of mim ic peptides.Then Ang1-7 was labeled with fluorescence to track their affinity for A549 cells,unlabeled molecules was used as competent control.The effect of peptides on A549 proliferation was assayed by MTT method.Re sults: The two angiotensin mimic peptides can apparently resist the degredation by ACE,NEP and LAP.They can specifically combine with A549 cells and can be competitively antagonized by unlabeled counterpart.Further more,both Ang1-7 and mimic peptides can inhibit the proliferation of A549 cells.Conclusion: We successfully constructed two Ang1-7 mimic peptides that can resist protease degradation,combined and inhibit the proliferation of A549 cells.The work laid a foundation for further study of anti-tumor effect of mimic peptides in animal mod els and evaluating their prospect of application.