1. ¹Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, PR China
2. ²Department of Surgery, Cancer Hospital, Fudan University, Shanghai 200032, PR China
3. ³Experimental Animal Center, Fudan University, Shanghai 200032, PR China
4. ⁴Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02138, USA
5. ⁵National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai 200032, PR China

Correspondence: Dr Cong-Jian Xu, MD, PhD, Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, 419 Fang-Xie Road, Shanghai 200011 PR China. E-mail: fckxu@vnet.citiz.net

Received 2 September 2004; Published online 20 May 2005.

Abstract

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, -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 -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 -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 (4.062.12 g) was much less than the group treated intravenously (18.258.34 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.