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 G1. Previous studies demonstrated its antiangiogenic effects in vitro and in vivo, and its antitumor activity in vivo. In this study, patientderived 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. © 2012 Landes Bioscience.