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

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) ta...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-05, Vol.64 (10), p.3365-3370
Main Authors: TAKEI, Yoshifumi, KADOMATSU, Kenji, YUZAWA, Yukio, MATSUO, Seiichi, MURAMATSU, Takashi
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Base Sequence
Biological and medical sciences
Cell Line, Tumor
Collagen - administration & dosage
Gene Transfer Techniques
Humans
Male
Medical sciences
Mice
Mice, Nude
Molecular Sequence Data
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - therapy
Pharmacology. Drug treatments
Prostatic Neoplasms - blood supply
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - therapy
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - genetics
Transfection
Tumors
Vascular Endothelial Growth Factor A - antagonists & inhibitors
Vascular Endothelial Growth Factor A - biosynthesis
Vascular Endothelial Growth Factor A - genetics
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-03-2682