Synergistic action of oncolytic herpes simplex virus and radiotherapy in pancreatic cancer cell lines.
BACKGROUND
Despite much research in chemotherapy and radiotherapy, pancreatic adenocarcinoma remains a fatal disease, highly resistant to all treatment modalities. Recent developments in the field of herpes simplex virus (HSV) engineering have allowed the generation of a number of promising virus vectors for treatment of many cancers, including pancreatic tumours. This study examined the use of one such virus, NV1023, in combination with radiation therapy in pancreatic cancer cell lines.


METHODS
HSV therapy in combination with radiotherapy was investigated in pancreatic cancer cell lines Hs766T, Panc-1 and MIA PaCa-2. Multiple therapy effect analysis was performed by computerized simulation. Mechanisms underlying synergy, such as virus replication and apoptosis, were investigated.


RESULTS
The combination of NV1023 and radiation yielded a synergistic oncolytic effect in all tested pancreatic cancer cell lines, with the greatest effect achieved in MIA PaCa-2. This effect was not mediated by an increase in rapid viral replication, but by a substantial increase in apoptosis.


CONCLUSIONS
The synergistic oncolytic actions of HSV and radiotherapy observed in pancreatic cancer cell lines encourage further testing of this multimodality treatment.
Dai
M-H
MH
Department of Surgery, Peking Union Medical College Hospital, Beijing, China.
Zamarin
D
D
Gao
S P
SP
Chou
T-C
TC
Gonzalez
L
L
Lin
S-F
SF
Fong
Y
Y
D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D017209:Apoptosis; D002470:Cell Survival; D004396:Coloring Agents; D003131:Combined Modality Therapy; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D005720:Gamma Rays / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human; D006801:Humans; D020287:In Situ Nick-End Labeling; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D011419:Propidium; D018139:Simplexvirus; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000528:radiation effects
D004396:Coloring Agents; D011419:Propidium; D004253:DNA Nucleotidylexotransferase