TY - JOUR
T1 - Therapy of human ovarian cancer by transfection with the murine interferon β gene
T2 - Role of macrophage-inducible nitric oxide synthase
AU - Xu, Lei
AU - Xie, Keping
AU - Fidler, Isaiah J.
PY - 1998/12/10
Y1 - 1998/12/10
N2 - The purpose of this study was to determine whether the local sustained production of murine interferon β (mIFN-β) 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-β (Hey-β) 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-β-transfected cells did not produce any tumors. The IFN-β-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-β-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-β 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.
AB - The purpose of this study was to determine whether the local sustained production of murine interferon β (mIFN-β) 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-β (Hey-β) 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-β-transfected cells did not produce any tumors. The IFN-β-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-β-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-β 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.
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U2 - 10.1089/hum.1998.9.18-2699
DO - 10.1089/hum.1998.9.18-2699
M3 - Article
C2 - 9874268
AN - SCOPUS:0032506770
SN - 1043-0342
VL - 9
SP - 2699
EP - 2708
JO - Human gene therapy
JF - Human gene therapy
IS - 18
ER -