Enhanced efficiency and specificity of ovarian cancer gene therapy in rats with a novel nonviral gene delivery system (GE7) via intraovarian artery perfusion approach

Abstract

Transfer of the herpes simplex virus type I-thymidine kinase gene, followed by the administration of ganciclovir (HSV 1 -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 HSV 1 -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, b-gal gene, as well as HSV 1 -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 b-gal and HSV 1 -tk in tumors were significantly stronger than those expressed in such organs as the hearts, livers, spleens, lungs and kidneys. However, no b-gal and HSV 1 -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 (4.0672.12 g) was much less than the group treated intravenously (18.2578.34 g) (Po.01). These findings indicated that the administration of GE7/HSV 1 -tk complex via the ovarian artery route could be a promising avenue of future human ovarian cancer treatment.

High-level transgene expression mediated by the piggyBac transposon enhances transgenic therapeutic effects in cervical cancer xenografts

“…One interesting observation in this study is that there were many more tumor cells in the S-phase of the cell cycle in the PB/TK group than the control groups. We also observed similar results in a previous study involving ovarian cancer (31). This suggested that the HSV-tk/GCV system combined with S-phase targeted chemotherapy may enhance suicide gene therapy in cancer.…”

Gene therapy for ovarian cancer

“…This same group also noted the importance of protecting siRNA through a vector in order to circumvent complete degradation of naked siRNA following intraperitoneal injection [21]. A novel nonviral gene delivery system, GE7, was recently reported by Jiang et al [22] to effectively transfer HSV1-tk (herpes simplex virus thymidine kinase) genes administered through ovarian arteries in rats with ovarian transplants. This system was much more effective than venous administration of the same construct.…”