Antitumor effect of FP3 on a patient-derived tumor tissue xenograft model of rectal carcinoma.
OBJECTIVE
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.


METHODS
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.
Tienan
T
Bi
Tienan
T
Bi
Huanrong
H
Lan
Xinxia
X
Hu
Min
M
Zhu
Zhenzhen
Z
Xu
Jinxi
J
Hu
Lisong
L
Teng
Ketao
K
Jin
D002288:Adenocarcinoma, Mucinous / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000068258:Bevacizumab; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D012004:Rectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C557495:FP3 VEGF receptor Fc-fusion protein; D018809:Proliferating Cell Nuclear Antigen; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab