Antitumor activities of Liver-targeting peptide modified Recombinant human Endostatin in BALB/c-nu mice with Hepatocellular carcinoma.

Antitumor activities of Liver-targeting peptide modified Recombinant human Endostatin in BALB/c-nu mice with Hepatocellular carcinoma.
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肝靶向肽修饰的重组人内皮抑素对患有肝细胞癌的 BALB/c-nu 小鼠的抗肿瘤活性

DOI:
10.1038/s41598-017-14320-0
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发表时间:
2017-10-26
期刊:
影响因子:
4.6
通讯作者:
Jiayong Z
Jiayong Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yan M;Dongmei B;Jingjing Z;Xiaobao J;Jie W;Yan W;Jiayong Z

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本课题组在前期研究中构建了肝靶向肽CSP I-plus修饰的重组人内皮抑素(rEndostatin,endostar)(rES-CSP),并在体外显示出较强的抗血管生成能力,能特异性地与人肝癌细胞结合,产生直接的抑制作用。本研究采用人肝癌细胞株HepG 2裸鼠皮下移植瘤模型和裸鼠原位移植瘤模型,对rES-CSP的生物学活性进行了评价。我们发现,与对照组相比,rES-CSP在皮下异种移植的裸鼠中显著减小肿瘤体积至54.9%。在原位移植瘤模型中,rES-CSP不仅使肿瘤体积减小(与对照组相比为39.6%)和肿瘤重量减小,而且还增加了其在肝组织和肝癌组织中的生物分布。肿瘤组织中微血管密度(MVD)较低,凋亡指数(AI)较高。对小鼠的心、肝、脾、肺、肾无明显毒副作用。结果表明CSP I-plus修饰的Endostar有望成为肝癌靶向治疗的候选药物。
In our previous study, a liver-targeting peptide CSP I-plus modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed and showed potent antiangiogenic capability and could specifically bind to human hepatocellular carcinoma cells to make a direct inhibitionin vitro. In this study, the biological activities of rES-CSPin vivowere evaluated by subcutaneous and orthotopic xenograft nude mice model of human hepatocellular carcinoma cells HepG2. We found that rES-CSP significantly decreased tumor volume to 54.9% in the nude mice with subcutaneous xenograft compared with the control. In orthotopic xenograft model, rES-CSP not only decreased tumor volume (to 39.6% compared with the control) and tumor weight, it also increased its biodistribution in the liver tissue and hepatoma tissue. Moreover, lower microvessel density (MVD) and higher apoptotic index (AI) were also observed in the tumor tissues. It had no significant side-effects on the heart, liver, spleen, lung and kidney of mice. Results indicated CSP I-plus modified Endostar may be a potential candidate for a targeting therapy on hepatocellular carcinoma.
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