Intraperitoneal injection of adenovirus expressing antisense K-ras RNA suppresses peritoneal dissemination of hamster syngeneic pancreatic cancer without systemic toxicity

We examined the antitumor effect and safety of the adenovirus-mediated expression of antisense K-ras RNA in two peritoneal dissemination models of pancreatic cancer. First, we found that the infection of an adenovirus vector expressing antisense human K-ras RNA (AxCA-AS) induced significant apoptosis in vitro in human pancreatic cancer cells with K-ras mutation. Second, the intraperitoneal (ip) injection of AxCA-AS effectively suppressed the growth of human pancreatic cancer cells in the peritoneal cavity of nude mice. Third, in the hamster syngeneic peritoneal dissemination model, the ip injection of an adenovirus expressing antisense hamster K-ras RNA significantly suppressed the peritoneal growth of hamster pancreatic cancer cells, and no significant systemic toxicity was observed in the treated hamsters. This study suggests a feasibility of the development of a therapeutic strategy against pancreatic cancer based on the adenovirus-mediated transduction of an antisense K-ras construct. (C) 2004 Elsevier Ireland Ltd. All rights reserved.