The aim of the present study was to investigate the effects of urantide on the expression status of C-reactive protein (CRP) and the inflammatory cytokines monocyte chemotactic protein (MCP)-1 and transforming growth factor (TGF)-β in the aortas of rats with atherosclerosis (AS), and to identify its underlying mechanisms. The effects of urantide in a rat model of AS and in cultured rat vascular smooth muscle cells (VSMCs) were analyzed via hematoxylin and eosin staining, immunohistochemical staining and ELISA. The results in vivo demonstrated that urantide downregulated the expression of inflammatory mediators CRP and MCP-1 and upregulated the expression of TGF-β. The results in vitro indicated that urantide inhibited the proliferation of VSMCs. In addition, urantide reduced the expression of CRP and downregulated the secretion of TGF-β in the culture supernatant. In conclusion, urantide ameliorated the arterial inflammatory damage that was observed in the AS rat model at the cell and tissue levels by controlling the expression of CRP and the inflammatory cytokines MCP-1 and TGF-β. Therefore, urantide may be a potential agent for the complementary treatment of AS.

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Overexpression of gonadotropin-releasing hormone (GnRH) receptor in many tumors but not in normal tissues makes it possible to use GnRH analogs as targeting peptides for selective delivery of cytotoxic agents, which may help to enhance the uptake of anticancer drugs by cancer cells and reduce toxicity to normal cells. The GnRH analogs [D-Cys 6 , desGly 10 , Pro 9 -NH 2 ]-GnRH, [D-Cys 6 , desGly 10 , Pro 9 -NHEt]-GnRH, and [D-Cys 6 , α-aza-Gly 10 -NH 2 ]-GnRH were conjugated with doxorubicin (Dox), respectively, through N-succinimidyl-3-maleimidopropionate as a linker to afford three new GnRH-Dox conjugates. The metabolic stability of these conjugates in human serum was determined by RP-HPLC. The antiproliferative activity of the conjugates was examined in GnRH receptor-positive MCF-7 human breast cancer cell line by MTT assay. The three GnRH-Dox conjugates showed improved metabolic stability in human serum in comparison with AN-152. The antiproliferative effect of conjugate II ([D-Cys 6 , desGly 10 , Pro 9 -NHEt]-GnRH-Dox) on MCF-7 cells was higher than that of conjugate I ([D-Cys 6 , desGly 10 , Pro 9 -NH 2 ]-GnRH-Dox) and conjugate III ([D-Cys 6 , α-aza-Gly 10 -NH 2 ]-GnRH-Dox), and the cytotoxicity of conjugate II against GnRH receptor-negative 3T3 mouse embryo fibroblast cells was decreased in comparison with free Dox. GnRH receptor inhibition test suggested that the antiproliferative activity of conjugate II might be due to the cellular uptake mediated by the targeting binding of [D-Cys 6 -des-Gly 10 -Pro 9 -NHEt]-GnRH to GnRH receptors. Our study indicates that targeting delivery of conjugate II mediated by [D-Cys 6 -des-Gly 10 -Pro 9 -NHEt]-GnRH is a promising strategy for chemotherapy of tumors that overexpress GnRH receptors.

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