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.
Son
K
K
Department of Pharmaceutics, Rutgers, State University of New Jersey, College of Pharmacy, Piscataway 08855, USA.
D000818:Animals; D001201:Ascites / Q000276:immunology / Q000473:pathology; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis; D009569:Nitric Oxide / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured
D011993:Recombinant Fusion Proteins; D009569:Nitric Oxide; D007371:Interferon-gamma; D015500:Chloramphenicol O-Acetyltransferase; D002945:Cisplatin