Enhanced efficiency and specificity of ovarian cancer gene therapy in rats with a novel nonviral gene delivery system (GE7) via intraovarian artery perfusion approach.
Transfer of the herpes simplex virus type I-thymidine kinase gene, followed by the administration of ganciclovir (HSV1-tk/GCV) into ovarian cancer-derived cell line either in vitro or transplanted into nude mice has been shown to provide a potential strategy for the gene therapy of ovarian cancer. We investigated the antitumor effects of HSV1-tk/GCV strategy with a chemically induced rat ovarian cancer model and a tumor-selective gene delivery by a novel nonviral gene delivery system (GE7) through the ovarian artery and tail vein. We demonstrated the expression of a reporter gene, beta-gal gene, as well as HSV1-tk gene in tumors and other organs, evaluated the overall antitumor effects after the GCV treatment and analyzed the tumor cell cycle phase distribution. Via the ovarian artery route, the expressions of beta-gal and HSV1-tk in tumors were significantly stronger than those expressed in such organs as the hearts, livers, spleens, lungs and kidneys. However, no beta-gal and HSV1-tk were detected in the tumor tissues when administrated via the tail vein, and little was found in other organs. The cell cycle analysis showed that the total S-phase of tumor cells in the test intra-arterial treatment group was considerably higher than that of the controls. The weight of the tumor tissues in the group treated by the intra-arterial route (4.06+/-2.12 g) was much less than the group treated intravenously (18.25+/-8.34 g) (P<.01). These findings indicated that the administration of GE7/HSV1-tk complex via the ovarian artery route could be a promising avenue of future human ovarian cancer treatment.
Jiang
Wei
W
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, PR China.
Xu
Cong-Jian
CJ
Shao
Zhi-Min
ZM
Zhou
Wen-Jiang
WJ
Ye
Bin
B
Tian
Pei-Kun
PK
Zhu
Jin-De
JD
Gu
Jian-Ren
JR
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D015774:Ganciclovir / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase
D017931:DNA Primers; D015127:9,10-Dimethyl-1,2-benzanthracene; D013937:Thymidine Kinase; D001616:beta-Galactosidase; D015774:Ganciclovir