Inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23H1 in an orthotopic implantation model.
Ovarian cancer is one of the most threatening malignant tumors in females due to the frequent occurrence of metastasis that precedes diagnosis. The present study explored the possibility of preventing ovarian cancer metastasis by promoting nm23H1 expression through adeno-associated virus (AAV)-mediated gene transfer. A cell line of high metastatic potential, SW626-M4, was derived by in vivo selection and used to establish an ovarian cancer metastasis model in the mouse. Liver metastasis and animal survival time were measured after transfer of a recombinant adeno-associated viral vector expressing nm23H1 (AAV-nm23H1) into the aforementioned model. Intraperitoneal injection of AAV-nm23H1 into this orthotopic implantation model of ovarian cancer resulted in (1) expression of the exogenous gene in more than 95% of tumor cells in situ in nude mice; (2) a 60% reduction in the number of animals developing liver metastases; and (3) a 35-day prolongation of median survival time compared with the untreated host group. In conclusion, the results support the feasibility of induction of nm23H1 expression through gene transfer as a therapeutic strategy for preventing metastases and prolonging host survival time, and indicate that AAV vectors deserve attention in the design of future gene therapy approaches to achieving long-term expression of curative genes in vivo.
Li
J
J
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, PR China.
Zhou
J
J
Chen
G
G
Wang
H
H
Wang
S
S
Xing
H
H
Gao
Q
Q
Lu
Y
Y
He
Y
Y
Ma
D
D
D000230:Adenocarcinoma / Q000235:genetics / Q000556:secondary / Q000628:therapy; D000818:Animals; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016133:Polymerase Chain Reaction
D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase