Kamiyama Masako, Ichikawa Yasushi, Ishikawa Takashi, Chishima Takashi, Hasegawa Satoshi, Hamaguchi Yohei, Nagashima Yoji, Miyagi Yohei, Mitsuhashi Masato, Hyndman David, Hoffman Robert M, Ohki Shigeo, Shimada Hiroshi
Department of Surgery II, Yokohama City University, School of Medicine, Yokohama, Japan.
Cancer Gene Ther. 2002 Feb;9(2):197-201. doi: 10.1038/sj.cgt.7700428.
The efficacy of a phosphorothioate antisense oligonucleotide (ASO) for KDR/Flk-1 (KDR/Flk-1-ASO), an endothelial cell-specific vascular endothelial growth factor (VEGF) receptor, was investigated on the peritoneal dissemination and angiogenesis of a human gastric cancer cell line in nude mice. Green fluorescent protein (GFP)-transduced NUGC-4 (NUGC-4-GFP) human gastric cancer cells were implanted into the peritoneal cavity of nude mice. KDR/Flk-1-ASO, -SO, or phosphate-buffered saline was administrated from days 7 to 14, 200 microg/mouse, once a day. The mice were sacrificed on day 28. Disseminated peritoneal tumor nodules expressing GFP were visualized by fluorescence microscopy. KDR/Flk-1-ASO significantly decreased the extent of peritoneal dissemination of the tumors. The number of cells undergoing apoptosis was significantly increased in the KDR/Flk-1-ASO-treated tumors. Microvessel density was significantly reduced in the KDR/Flk-1-ASO-treated tumor nodules. The KDR/Flk-1 antisense strategy, therefore, decreases tumor dissemination apparently by inhibiting angiogenesis.
