Oncolytic viral therapy for human pancreatic cancer cells by reovirus.
OBJECTIVE
Pancreatic cancer has a poor prognosis and few effective therapies are available. The oncolytic effect of reovirus has been observed in cancer cells with an activated Ras signaling pathway, and pancreatic cancer may be a candidate target for reovirus because K-ras mutation is frequently found in pancreatic cancer.


METHODS
In this study, we examined the feasibility of using reovirus (serotype 3) as an antihuman pancreatic cancer agent.


RESULTS
Reovirus was able to infect five human pancreatic cancer cell lines (Panc1, MIApaca-2, PK1, PK9, and BxPC3) in vitro. We also confirmed that the Ras activity in these cancer cell lines was elevated compared with that in the normal cell line and that susceptibility to reovirus was associated with the Ras activity of these cells. In a unilateral murine xenograft model using Panc1 and BxPC3 cell lines, each tumor growth was suppressed by intratumoral injection of reovirus. Furthermore, local injection of reovirus also had systemic antitumor effects in a bilateral xenograft model using Panc1 cell line. Immunohistochemical examination revealed that reovirus replication was observed within the tumor but not in surrounding normal tissue.


CONCLUSIONS
These results suggest that reovirus can be considered for a novel therapy against pancreatic cancer.
Etoh
Tsuyoshi
T
Department of Surgery I, Faculty of Medicine, Oita Medical University, Hasamamachi 1-1, Oita 879-5593, Japan. teto@oita-med.ac.jp
Himeno
Yoshihisa
Y
Matsumoto
Toshifumi
T
Aramaki
Masanori
M
Kawano
Katsunori
K
Nishizono
Akira
A
Kitano
Seigo
S
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000628:therapy*; D012087:Reoviridae / Q000235:genetics*; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000378:metabolism
D018631:ras Proteins