HAMSTER PANCREATIC CANCER MODEL FOR EXPERIMENTAL THERAPEUTIC TRIALS

Abstract

Background: The experimental model of the pancreatic cancer induced by N-nitorosobis(2-oxopropyl)amine (BOP) in Syrian golden hamsters is very useful for investigating the pancreatic cancer. We developed short-term pancreatic cancer models in hamsters using an established pancreatic cancer cell line (PGHAM-1) and estimated the utility of the models. Methods: With three PGHAM-1 models; 1) primary pancreatic cancer and simultaneous liver metastasis by intrapancreatic transplantation, 2) liver metastasis alone by intrasplenic transplantation, 3) peritoneal dissemination by intraperitoneal transplantation, within twenty-one days after inoculation, we studied the effect of several anti-angiogenic substances (angiostatin, tranilast, thalidomide, TNP-470, MMI-166) on primary and metastatic pancreatic tumors. The incidence, size, diameter, microvessel density (MVD), apoptotic index (AI), and AgNOR score of the primary and metastatic tumors were examined. In addition, PGHAM-1-Luc-1, which is luciferase-positive PGHAM-1 cells, was newly developed and served for feasibility study. Resutls: All of anti-angiogenic substances were proved to have inhibitory effect on pancreatic cancer by reduction of size and incidence of primary tumor and metastasis, decreased angiogenesis and increased apoptosis. Proliferative activity was not influenced by those agents. By using PGHAM-1-Luc-1, we can detect the primary tumor and its metastasis by administration ofluciferin in IVIS imaging system (Xenogen) and investigate the metastaticprocess of pancreatic cancer without sacrificing the animals. Conclusions: These models would be suitable not only for study of pathogenesis of pancreatic cancer and its metastasis but also for one of preclinical trials of chemotherapeutic agents such as anti-angiogenic substances.