Vascular Endothelial Growth Factor Accelerates Establishment of a Model of Hepatic Metastasis in Walker-256 Tumor-Bearing Rats

Abstract

BackgroundAnimal models of secondary liver cancer are limited by the time required for the development of hepatic metastases. The authors administered vascular endothelial growth factor (VEGF) to stimulate tumor growth in a model of hepatic metastasis. MethodsA 0.5 to 1.0 mm3 Walker-256 carcinosarcoma tumor tissue was implanted into the livers of 45 Sprague–Dawley rats, randomly assigned to 3 equal groups to receive daily injections (0.1 mL), for 1 week, of either normal saline (control group), 20 mg/L VEGF (VEGF-20 group) or 40 mg/L VEGF (VEGF-40 group). Tumor growth was assessed by magnetic resonance imaging after 3, 7 and 14 days, and overall survival was recorded. ResultsThree days after implantation, no tumors were detected by magnetic resonance imaging in the control group. in contrast, tumors were observed in 50% of rats in the VEGF-20 group and 66.7% of rats in the VEGF-40 group (P < 0.05). By day 7, tumors were detected in 92.8% of rats in the VEGF-20 group, 86.7% of rats in the VEGF-40 group, but only 21.4% of rats in the control group (P < 0.05). Tumor size increased progressively, reaching 1.81 ± 0.08, 2.51 ± 0.12 and 2.67 ± 0.10 cm3 in the control, VEGF-20 and VEGF-40 groups, respectively, 14 days after implantation of tumor tissue. Median survival times were significantly shorter in the VEGF-40 group (15 days) than in the control and VEGF-20 groups (27 and 25, respectively) (both P < 0.05). ConclusionsDaily VEGF injection (20 mg/L, 1 week) accelerates tumorigenesis without compromising survival, potentially extending the period in which experiments can be conducted in this model.