Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
Pharmacy, Shexian People's Hospital, Huangshan, Anhui, 245200, People's Republic of China.
Sci Rep. 2017 Oct 26;7(1):14074. doi: 10.1038/s41598-017-14320-0.
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 inhibition in vitro. In this study, the biological activities of rES-CSP in vivo were 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.
在我们之前的研究中，构建了一种肝靶向肽 CSP I-Plus 修饰的重组人血管内皮抑制素（rEndostatin，endostar）（rES-CSP），其具有很强的抗血管生成能力，并能特异性与人肝癌细胞结合，在体外直接抑制。在这项研究中，通过皮下和原位异种移植裸鼠模型的人肝癌细胞 HepG2 评估了 rES-CSP 的体内生物学活性。我们发现，与对照组相比，rES-CSP 使裸鼠皮下异种移植模型中的肿瘤体积显著减小至 54.9%。在原位异种移植模型中，rES-CSP 不仅降低了肿瘤体积（与对照组相比减少了 39.6%）和肿瘤重量，还增加了其在肝组织和肝癌组织中的生物分布。此外，肿瘤组织中还观察到较低的微血管密度（MVD）和较高的凋亡指数（AI）。它对小鼠的心、肝、脾、肺和肾没有明显的副作用。结果表明，CSP I-Plus 修饰的血管内皮抑制素可能是肝癌靶向治疗的潜在候选药物。
