Adenovirus-mediated delivery of human IFNγ gene inhibits prostate cancer growth

被引:21
作者
Zhao, Peng
Zhu, Ying-Hui
Wu, Jiang-Xue
Liu, Ran-Yi
Zhu, Xiu-Yun
Xiao, Xia
Li, Hong-Li
Huang, Bi-Jun
Xie, Fa-Jun
Chen, Jie-Min
Ke, Miao-La
Huang, Wenlin [1 ]
机构
[1] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510060, Peoples R China
[2] Chinese Acad Sci, Inst Microbiol, Beijing 100080, Peoples R China
关键词
prostate cancer; IFN gamma; gene therapy; adenoviral vector;
D O I
10.1016/j.lfs.2007.05.028
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Interferon gamma (IFN-gamma) is regarded as a potent antitumor agent, but therapy with IFN-gamma is hampered by its short half-life and significant side effects. We developed a replication defective adenovirus carrying the human IFN-gamma gene and evaluated the effects of adenovirus-mediated IFN-gamma (Ad-IFN-gamma) gene transfer on human prostate cancer cell lines in vitro and on xenografts in vivo. Our results showed infection of prostate cancer cells with Ad-IFN-gamma led to production of an active cytokine and resulted in an antiproliferative effect on the prostate cancer cells. Intraturnoral injection of Ad-IFN-gamma significantly inhibited the growth of DU-145 cell xenografts in vivo, while no significant toxicity effect was observed. RT-PCR analysis indicated transgene expression mainly enriched in tumors in vivo, and slightly distributed in livers. These findings suggest adenovirus-mediated IFN-gamma gene transfer is a promising approach in the treatment of advanced prostate cancer. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:695 / 701
页数:7
相关论文
共 28 条
[1]   Peptide mimotics of gamma interferon possess antiviral properties against vaccinia virus and other viruses in the presence of poxvirus B8R protein [J].
Ahmed, CMI ;
Burkhart, MA ;
Subramaniam, PS ;
Mujtaba, MG ;
Johnson, HM .
JOURNAL OF VIROLOGY, 2005, 79 (09) :5632-5639
[2]   Cellular responses to interferon-gamma [J].
Boehm, U ;
Klamp, T ;
Groot, M ;
Howard, JC .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :749-795
[3]  
CAMAUD C, 1999, J IMMUNOL, V163, P4647
[4]   Targeted delivery of IFNγ to tumor vessels uncouples antitumor from counterregulatory mechanisms [J].
Curnis, F ;
Gasparri, A ;
Sacchi, A ;
Cattaneo, A ;
Magni, F ;
Corti, A .
CANCER RESEARCH, 2005, 65 (07) :2906-2913
[5]   A history of prostate cancer treatment [J].
Denmeade, SR ;
Isaacs, JT .
NATURE REVIEWS CANCER, 2002, 2 (05) :389-396
[6]   Interferon γ inhibits growth of human pancreatic carcinoma cells via caspase-1 dependent induction of apoptosis [J].
Detjen, KM ;
Farwig, K ;
Welzel, M ;
Wiedenmann, B ;
Rosewicz, S .
GUT, 2001, 49 (02) :251-262
[7]   Adenovirus-mediated intralesional interferon-γ gene transfer induces tumor regressions in cutaneous lymphomas [J].
Dummer, R ;
Hassel, JC ;
Fellenberg, F ;
Eichmüller, S ;
Maier, T ;
Slos, P ;
Acres, B ;
Bleuzen, P ;
Bataille, V ;
Squiban, P ;
Burg, G ;
Urosevic, M .
BLOOD, 2004, 104 (06) :1631-1638
[8]   IFN unresponsiveness in LNCaP cells due to the lack of JAK1 gene expression [J].
Dunn, GP ;
Sheehan, KCF ;
Old, LJ ;
Schreiber, RD .
CANCER RESEARCH, 2005, 65 (08) :3447-3453
[9]   Gene transfer of IFN-γ into established brain tumors represses growth by antiangiogenesis [J].
Fathallah-Shaykh, HM ;
Zhao, LJ ;
Kafrouni, AI ;
Smith, GM ;
Forman, J .
JOURNAL OF IMMUNOLOGY, 2000, 164 (01) :217-222
[10]  
Gattacceca F, 2002, CLIN CANCER RES, V8, P3298