Cisplatin-based interferon gamma gene therapy of murine ovarian carcinoma

Cis-diamminedichloroplatinum(II) increased in vivo lipofection efficiency of tumor cells with a target gene, interferon gamma (IFN gamma), in a murine metastatic ovarian carcinoma model. The expression of IFN gamma gene in ascitic tumors reached a peak at day 11 after cisplatin treatment and lasted over 1 week. A local increase in IFN gamma gene expression increased a local expression of inducible nitric oxide synthase (iNOS) and the tumor necrosis factor a gene. This treatment suppressed tumor growth (or killed tumor cells) and increased the long-term survival of animals (at least 80 days) without tumors, which was prevented by simultaneous treatment of iNOS inhibitor aminoguanidine. The results indicate that cisplatin-based IFN gamma gene therapy is an effective treatment protocol and nitric oxide may play a major part for tumor cell killing or growth.