FP3对直肠癌患者来源的肿瘤组织异种移植模型的抗肿瘤作用。
Antitumor effect of FP3 on a patient-derived tumor tissue xenograft model of rectal carcinoma.
作者信息
Bi Tienan, Bi Tienan, Lan Huanrong, Hu Xinxia, Zhu Min, Xu Zhenzhen, Hu Jinxi, Teng Lisong, Jin Ketao
出版信息
Hepatogastroenterology. 2013 Nov-Dec;60(128):1950-4.
BACKGROUND/AIMS: FP3 is an engineered protein which contains the extracellular domain 2 of VEGF receptor 1 (Flt-1) and extracellular domain 3 and 4 of VEGF receptor 2 (Flk-1, KDR) fused to the Fc portion of human immunoglobulin G1. Previous studies demonstrated its antiangiogenic and antitumor effects in vitro and in vivo.
METHODOLOGY
In this study, a PDTT xenograft model of rectal carcinoma was established for assessment of the antitumor activity of FP3. Xenografts were treated with FP3 or bevacizumab (Avastin). After tumor growth was confirmed, volume and microvessel density in tumors were evaluated. Levels of VEGF and PCNA in the tumor were examined by immunohistonchemical staining and western blotting.
RESULTS
FP3 showed significant antitumor activity in the PDTT xenograft model of rectal carcinoma. The microvessel density in tumor tissues treated with FP3 was lower than that of the control. Antitumor activity of FP3 was similar to that of bevacizumab in the PDTT xenograft model of rectal carcinoma.
CONCLUSIONS
This study indicated that FP3 could be used as an effective antiangiogenic and antitumor agent in treatment of colorectal carcinoma.
背景/目的：FP3是一种工程蛋白，它包含血管内皮生长因子受体1（Flt-1）的细胞外结构域2以及血管内皮生长因子受体2（Flk-1，KDR）的细胞外结构域3和4，并与人免疫球蛋白G1的Fc部分融合。先前的研究已证实其在体外和体内均具有抗血管生成和抗肿瘤作用。
方法
在本研究中，建立了直肠癌的PDTT异种移植模型，以评估FP3的抗肿瘤活性。用FP3或贝伐单抗（阿瓦斯汀）处理异种移植瘤。在确认肿瘤生长后，评估肿瘤的体积和微血管密度。通过免疫组织化学染色和蛋白质印迹法检测肿瘤中VEGF和PCNA的水平。
结果
在直肠癌的PDTT异种移植模型中，FP3显示出显著的抗肿瘤活性。用FP3处理的肿瘤组织中的微血管密度低于对照组。在直肠癌的PDTT异种移植模型中，FP3的抗肿瘤活性与贝伐单抗相似。
结论
本研究表明，FP3可作为治疗结直肠癌的一种有效的抗血管生成和抗肿瘤药物。
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