Long-Term Local Injection of RAGE-Aptamer Suppresses the Growth of Malignant Melanoma in Nude Mice

Autor: Nobutaka Nakamura, Sho-ichi Yamagishi, Yuri Nishino, Takanori Matsui, Yuichiro Higashimoto, Ami Sotokawauchi
Rok vydání: 2019
Předmět:
Zdroj: Journal of Oncology, Vol 2019 (2019)
Journal of Oncology
ISSN: 1687-8469
1687-8450
DOI: 10.1155/2019/7387601
Popis: Accumulating evidence has suggested the pathological role of advanced glycation end products (AGEs) and their receptor RAGE axis in aging-associated disorders, including cancers. In this study, we examined the effects of local injection of RAGE-aptamer adjacent to the tumor on G361 melanoma growth in nude mice. We further investigated the effects of RAGE-aptamer on oxidative stress generation, RAGE, vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) gene expression inNε-(carboxymethyl)lysine (CML)-exposed G361 melanoma cellsin vitro. Local injection of RAGE-aptamer adjacent to the tumor dramatically decreased the growth of G361 melanoma in nude mice, which was associated with reduced expression of CML, RAGE, nitrotyrosine, VEGF, CD31, and von Willebrand factor, markers of endothelial cells in G361 tumors. Furthermore, RAGE-aptamer inhibited the binding of CML to V-domain of RAGE and blocked the CML-induced increases in oxidative stress generation, RAGE, VEGF, and MCP-1 mRNA levels in G361 melanoma cells. Our present findings suggest that long-term local injection of RAGE-aptamer adjacent to the tumor could inhibit melanoma growth in nude mice partly by suppressing tumor angiogenesis via blockade of the CML-RAGE interaction. Local injection of RAGE-aptamer may be a feasible therapeutic tool for the treatment of malignant melanoma.
Databáze: OpenAIRE