A small interfering RNA targeting vascular endothelial growth factor as cancer therapeutics

被引:321
作者
Takei, Y
Kadomatsu, K
Yuzawa, Y
Matsuo, S
Muramatsu, T
机构
[1] Nagoya Univ, Grad Sch Med, Dept Biochem, Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Clin Immunol Internal Med, Showa Ku, Nagoya, Aichi 4668550, Japan
关键词
D O I
10.1158/0008-5472.CAN-03-2682
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Vascular endothelial growth factor (VEGF) plays a critical role during normal embryonic angiogenesis and also in the pathological angiogenesis that occurs in a number of diseases, including cancer. We developed a novel VEGF blockade system using RNA interference. The small interfering RNA (siRNA) targeting human VEGF almost completely inhibited the secretion of VEGF in a human prostate cancer cell line, PC-3, whereas the control scramble siRNA showed no effects. The VEGF siRNA with atelocollagen dramatically suppressed tumor angiogenesis and tumor growth in a PC-3 s.c. xenograft model. Atelocollagen provided a beneficial delivering means by which stabilization and efficient transfection of the siRNA injected into the tumors were achieved.
引用
收藏
页码:3365 / 3370
页数:6
相关论文
共 18 条
  • [1] Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors
    Bergers, G
    Song, S
    Meyer-Morse, N
    Bergsland, E
    Hanahan, D
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (09) : 1287 - 1295
  • [2] Brekken RA, 2000, CANCER RES, V60, P5117
  • [3] Antisense RNA to the type I insulin-like growth factor receptor suppresses tumor growth and prevents invasion by rat prostate cancer cells in vivo
    Burfeind, P
    Chernicky, CL
    Rininsland, F
    Ilan, J
    Ilan, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (14) : 7263 - 7268
  • [4] Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
    Elbashir, SM
    Harborth, J
    Lendeckel, W
    Yalcin, A
    Weber, K
    Tuschl, T
    [J]. NATURE, 2001, 411 (6836) : 494 - 498
  • [5] Analysis of gene function in somatic mammalian cells using small interfering RNAs
    Elbashir, SM
    Harborth, J
    Weber, K
    Tuschl, T
    [J]. METHODS, 2002, 26 (02) : 199 - 213
  • [6] Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
    Fire, A
    Xu, SQ
    Montgomery, MK
    Kostas, SA
    Driver, SE
    Mello, CC
    [J]. NATURE, 1998, 391 (6669) : 806 - 811
  • [7] FOLKMAN J, 1971, NEW ENGL J MED, V285, P1182
  • [8] ANGIOGENESIS IN CANCER, VASCULAR, RHEUMATOID AND OTHER DISEASE
    FOLKMAN, J
    [J]. NATURE MEDICINE, 1995, 1 (01) : 27 - 31
  • [9] VEGF-Trap: A VEGF blocker with potent antitumor effects
    Holash, J
    Davis, S
    Papadopoulos, N
    Croll, SD
    Ho, L
    Russell, M
    Boland, P
    Leidich, R
    Hylton, D
    Burova, E
    Ioffe, E
    Huang, T
    Radziejewski, C
    Bailey, K
    Fandl, JP
    Daly, T
    Wiegand, SJ
    Yancopoulos, GD
    Rudge, JS
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (17) : 11393 - 11398
  • [10] Atelocollagen-based gene transfer in cells allows high-throughput screening of gene functions
    Honma, K
    Ochiya, T
    Nagahara, S
    Sano, A
    Yamamoto, H
    Hirai, K
    Aso, Y
    Terada, M
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 289 (05) : 1075 - 1081