Adenovirus-mediated interferon-ß gene therapy suppresses growth and metastasis of human prostate cancer in nude mice

被引：55

作者：

Cao, GW ^{[1
]}

Su, JD ^{[1
]}

Lu, WX ^{[1
]}

Zhang, FH ^{[1
]}

Zhao, GL ^{[1
]}

Marteralli, D ^{[1
]}

Dong, ZY ^{[1
]}

机构：

[1] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol 173, Houston, TX 77030 USA

来源：

CANCER GENE THERAPY | 2001年 / 8卷 / 07期

关键词：

interferon-ss; prostate cancer; adenoviral vectors; nitric oxide; angiogenesis;

D O I：

10.1038/sj.cgt.7700333

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The purpose of this study was to determine the effects of interferon-beta (IFN-beta) gene transfer on the growth of PC3MM2 human prostate cancer cells in nude mice. Intralesional delivery of an adenoviral vector encoding murine IFN-beta (AdIFN-beta), but not a vector encoding bacterial beta -galactosidase (AdLac Z), suppressed PC3MM2 tumors in a dose-dependent manner. At the highest dose (2x10(9) plaque-forming units, PFU), a single injection of AdIFN-beta (but not AdLac Z) suppressed orthotopic PC3MM2 tumors and development of metastasis by 80%, and eradicated the tumors in 20% of mice. Immunohistochemical staining showed that AdIFN-beta -treated tumors contained fewer microvessels, fewer proliferating cells, and more apoptotic cells than did the control tumors. Compared with controls, tumors injected with AdIFN-beta expressed higher levels of IFN-beta and inducible nitric oxide synthase (iNOS) and lower levels of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1). In vitro analysis indicated that expression of bFGF and TGF-beta1 in PC3MM2 cells could be suppressed by the nitric oxide donor sodium nitroprusside. These data suggest that intratumoral delivery of the IFN-beta gene with adenoviral vectors could be an effective therapy for prostate cancer and that tumor suppression by AdIFN-beta correlated with up-regulation of iNOS and down-regulation of angiogenesis.

引用

页码：497 / 505

页数：9

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