Therapy of human ovarian cancer by transfection with the murine interferon beta gene: role of macrophage-inducible nitric oxide synthase.
The purpose of this study was to determine whether the local sustained production of murine interferon beta (mIFN-beta) could inhibit the growth of human ovarian cancer cells in the peritoneal cavity of nude mice. Human ovarian tumor Hey-A8 cells transfected with mIFN-beta (Hey-beta) or a control neomycin resistance vector (Hey-Neo) grew well in culture. Tumor cells were injected into the peritoneal cavity or under the subcutis of nuce mice. Parental (wild-type) or control transfected cells produced large tumors, whereas mIFN-beta-transfected cells did not produce any tumors. The IFN-beta-transfected cells prevented the outgrowth of bystander parental, control-transfected cells, and another human ovarian tumor cell line, SKOV3i.p.1, in the peritoneal cavity of nude mice. The IFN-beta-transfected tumor cells stimulated a high level of nitric oxide (NO) production in murine macrophages under both in vitro and in vivo conditions, and only the NO-producing macrophages exhibited antitumor activity. Collectively, these results demonstrate that the local production of IFN-beta can inhibit the in vivo growth of human ovarian cancer cells by upregulating the expression of the inducible nitric oxide synthase (iNOS) gene in host macrophages.
Xu
L
L
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Xie
K
K
Fidler
I J
IJ
D000818:Animals; D018283:Cystadenocarcinoma, Papillary / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics*; D017737:Macrophages, Peritoneal / Q000201:enzymology; D051379:Mice; D008819:Mice, Nude; D009569:Nitric Oxide / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000628:therapy*; D014162:Transfection
D009569:Nitric Oxide; D016899:Interferon-beta