Efficacy of oncolytic reovirus against human gastric cancer with peritoneal metastasis in experimental animal model.
The prognosis of gastric cancer patients with peritoneal dissemination is extremely poor, and the development of an effective treatment is necessary. The aim of this study was to investigate the efficacy of oncolytic reovirus against peritoneal metastasis in human gastric cancer using an experimental animal model. Four human gastric cancer cell lines, including MKN45p, NUGC4, MKN7 and KatoIII, a normal NIH3T3 cell line as a control, and reovirus serotype 3, were used in this study. We evaluated the cytopathic effect of reovirus and the Ras activity in each gastric cancer cell line in vitro. To evaluate oncolytic efficacy in vivo, reovirus (1x10(8) PFU) was administered into the peritoneal cavity of nude mice on days 7, 8 and 9 after inoculation with MKN45p cells. Mean volume of ascites and the total number and weight of the peritoneal tumors were measured after sacrifice. After reovirus infection, cytopathic effect was observed in all four gastric cancer cell lines, but not in the control cells. Ras activation assay showed that Ras activity in all four gastric cancer cell lines increased to a higher level than that in the control cells. In the animal model experiments, mean volume of ascites and the total number and weight of the peritoneal tumors in the reovirus treatment group were significantly lower than those in the control group. In conclusions, intraperitoneal administration of reovirus could be useful as a new modality against peritoneal metastasis in gastric cancer.
Department of Surgery I, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan. kojik@oita-u.ac.jp
Koji
K
Kawaguchi
Tsuyoshi
T
Etoh
Kosuke
K
Suzuki
Marcelo Takahiro
MT
Mitui
Akira
A
Nishizono
Norio
N
Shiraishi
Seigo
S
Kitano
D000818:Animals; D002277:Carcinoma / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D012089:Mammalian orthoreovirus 3 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy*; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays