title: Antitumor effects of FP3 in combination with capecitabine on PDTT xenograft models of primary colon carcinoma and related lymphatic and hepatic metastases.
abstract: 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 G 1. Previous studies demonstrated its antiangiogenic effects in vitro and in vivo, and its antitumor activity in vivo. In this study, patient-derived tumor tissue (PDTT) xenograft models of primary colon carcinoma and lymphatic and hepatic metastases were established for assessment of the antitumor activity of FP3 in combination with capecitabine. Xenografts were treated with FP3, capecitabine, alone or in combination. After tumor growth was confirmed, volume and microvessel density in tumors were evaluated. Levels of VEGF, and PCNA in the tumor were examined by immunohistonchamical staining, level of thymidine phosphorylase (TP) was examined by ELISA, and levels of related cell signaling pathways proteins expression were examined by western blotting. FP3 in combination with capecitabine showed significant antitumor activity in three xenograft models (primary colon carcinoma, lymphatic metastasis, and hepatic metastasis). The microvessel density in tumor tissues treated with FP3 in combination with capecitabine was lower than that of the control. Antitumor activity of FP3 in combination with capecitabine was significantly higher than that of each agent alone in three xenograft models (primary colon carcinoma, lymphatic metastasis, and hepatic metastasis). This study indicated that addition of FP3 to capecitabine significantly improved tumor growth inhibition in the PDTT xenograft models of primary colon carcinoma and lymphatic and hepatic metastases.
authors.affiliation: Department of Surgical Oncology, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang, China.
authors.forename: Ketao
authors.initials: K
authors.lastname: Jin
authors.forename: Huanrong
authors.initials: H
authors.lastname: Lan
authors.forename: Bojian
authors.initials: B
authors.lastname: Xie
authors.forename: Kuifeng
authors.initials: K
authors.lastname: He
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Xu
authors.forename: Guangliang
authors.initials: G
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Han
authors.forename: Lisong
authors.initials: L
authors.lastname: Teng
authors.forename: Feilin
authors.initials: F
authors.lastname: Cao
mesh_terms: D000328:Adult; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D000069287:Capecitabine; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000000981:diagnostic imaging / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011859:Radiography; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D013939:Thymidine Phosphorylase; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: 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; D003841:Deoxycytidine; D000069287:Capecitabine; D013939:Thymidine Phosphorylase; D005472:Fluorouracil