An Aptamer-Based Antagonist against the Receptor for Advanced Glycation End-Products (RAGE) Blocks Development of Colorectal Cancer

Tumor angiogenesis plays a crucial role in colorectal cancer development. Dysregulation of the receptor for the advanced glycation end-products (RAGE) transmembrane signaling mediates inflammation, resulting in various cancers. However, the mechanism of the RAGE signaling pathway in modulating development of colorectal cancer has not been explored. In this study, an aptamer-based RAGE antagonist (Apt-RAGE) was used to inhibit interaction between RAGE and S100B, thus blocking downstream NF kappa B-mediated signal transduction. In vitro results showed that Apt-RAGE effectively inhibited S100B-dependent and S100B-independent RAGE/NF kappa B activation in colorectal HCT116 cancer cells, thus decreasing proliferation and migration of cells. Notably, expression and secretion of VEGF-A were inhibited, implying that Apt-RAGE can be used as an antiangiogenesis agent in tumor therapy. Moreover, Apt-RAGE inhibited tumor growth and microvasculature formation in colorectal tumor-bearing mice. Inhibition of angiogenesis by Apt-RAGE was positively correlated with suppression of the RAGE/NF kappa B/VEGF-A signaling. The findings of this study show that Apt-RAGE antagonist is a potential therapeutic agent for treatment of colorectal cancer.

Automated summary

Tumor angiogenesis is crucial in colorectal cancer development, and dysregulation of the receptor for the advanced glycation end-products (RAGE) signaling mediates inflammation leading to various cancers. This study revealed that an aptamer-based RAGE antagonist (Apt-RAGE) effectively inhibited RAGE/NF kappa B activation in colorectal cancer cells, decreasing proliferation and migration and inhibiting VEGF-A expression and secretion. The findings suggest that Apt-RAGE could be a potential therapeutic agent for colorectal cancer treatment through antiangiogenic effects.