VIP Antagonist is a novel, orally active vasoactive intestinal peptide (VIP) receptor antagonist[1-2]. VIP Antagonist can be used in research related to inflammation, cancer, antiviral applications, among others[3-4].
In vitro, NCI-H838 non-small cell lung cancer (NSCLC) cells were incubated with VIP Antagonist (10μM) and stimulated with VIP (100nM) for 2 weeks. VIP Antagonist significantly inhibited VIP-stimulated colony formation while reducing the elevation in cAMP levels induced by VIP[5]. Human glioblastoma cells (e.g., U87, U118, U373) were treated with VIP Antagonist (1–10μM) and PACAP-27 for 5 days. VIP Antagonist inhibited the PACAP-27-induced increases in cAMP and cytosolic Ca²⁺ and significantly suppressed cell proliferation[6].
In vivo, C57BL/6 and BALB/c mice received daily subcutaneous injections of VIP Antagonist (10μg per mouse) for one week, starting one day before infection with murine cytomegalovirus (mCMV). VIP Antagonist significantly improved the survival rate of infected mice, reduced viral load in the liver and lungs, and decreased inflammatory pathological damage in these organs[7]. C57BL/6 wild-type mice with colitis induced by drinking 2.5% dextran sodium sulfate (DSS) were treated with VIP Antagonist (0.1-1μM; 200μL) from day 0 to day 11. VIP Antagonist significantly alleviated the clinical symptoms, histopathological damage, and expression of pro-inflammatory cytokines associated with DSS-induced colitis[8].
References:
[1] Moody TW, Jensen RT, Fridkin M, et al. (N-stearyl, norleucine17)VIPhybrid is a broad spectrum vasoactive intestinal peptide receptor antagonist. J Mol Neurosci. 2002 Feb-Apr;18(1-2):29-35.
[2] Li JM, Petersen CT, Li JX, et al. Modulation of Immune Checkpoints and Graft-versus-Leukemia in Allogeneic Transplants by Antagonizing Vasoactive Intestinal Peptide Signaling. Cancer Res. 2016 Dec 1;76(23):6802-6815.
[3] Petersen CT, Li JM, Waller EK. Administration of a vasoactive intestinal peptide antagonist enhances the autologous anti-leukemia T cell response in murine models of acute leukemia. Oncoimmunology. 2017 Mar 16;6(5):e1304336.
[4] Moody TW, Hill JM, Jensen RT. VIP as a trophic factor in the CNS and cancer cells. Peptides. 2003 Jan;24(1):163-77.
[5] Moody TW, Zia F, Draoui M, et al. A vasoactive intestinal peptide antagonist inhibits non-small cell lung cancer growth. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4345-9.
[6] Sharma A, Walters J, Gozes Y, et al. A vasoactive intestinal peptide antagonist inhibits the growth of glioblastoma cells. J Mol Neurosci. 2001 Dec;17(3):331-9.
[7] Li JM, Darlak KA, Southerland L, et al. VIPhyb, an antagonist of vasoactive intestinal peptide receptor, enhances cellular antiviral immunity in murine cytomegalovirus infected mice. PLoS One. 2013 May 27;8(5):e63381.
[8] Vu JP, Million M, Larauche M, et al. Inhibition of vasoactive intestinal polypeptide (VIP) induces resistance to dextran sodium sulfate (DSS)-induced colitis in mice. J Mol Neurosci. 2014 Jan;52(1):37-47.
VIP Antagonist是一种新型的、具有口服活性的血管活性肠肽（VIP）受体拮抗剂[1-2]。VIP Antagonist可用于炎症、癌症、抗病毒等相关研究[3-4]。
在体外，VIP Antagonist（10μM）与VIP（100nM）刺激非小细胞肺癌（NSCLC）细胞系NCI-H838 2周。VIP Antagonist显著抑制由VIP刺激的集落形成，同时降低由VIP引起的cAMP水平升高[5]。VIP Antagonist（1–10μM）与PACAP-27处理人胶质母细胞瘤细胞（如U87、U118、U373）5天。VIP Antagonist可抑制PACAP-27引起的cAMP升高和胞质Ca2+升高，并显著抑制细胞增殖[6]。
在体内，VIP Antagonist（10μg/只小鼠）每日一次皮下注射，用于处理C57BL/6和BALB/c小鼠，从感染巨细胞病毒（mCMV）前一天开始，持续一周。VIP Antagonist显著提高了感染小鼠的存活率，降低了肝脏和肺部的病毒载量，同时减少了这些器官的炎症病理损伤[7]。VIP Antagonist（0.1-1μM；200μL）用于处理饮用2.5%葡聚糖硫酸钠（DSS）诱导结肠炎的C57BL/6野生型小鼠，从第0天持续至第11天。VIP Antagonist显著减轻了DSS诱导的结肠炎临床症状、组织病理学损伤及促炎细胞因子表达[8]。