Tyr-Gly-Gly-Phe-Met-OH (Met-Enkephalin) is an endogenous opioid that acts as the δ opioid receptor with an EC50 value of 1.03nM[1]. Tyr-Gly-Gly-Phe-Met-OH can induce changes in macrophage function, stimulate the phagocytic activity of macrophages, and enhance the production of cytokines by macrophages[2]. Tyr-Gly-Gly-Phe-Met-OH can serve as a biomarker for stress-induced changes in the brain in mouse models[3].
In vitro, Tyr-Gly-Gly-Phe-Met-OH treatment (0.1nM) for 24h combined with IFN-γ caused an increase in IL-6 release from the cultured murine macrophages[4]. Tyr-Gly-Gly-Phe-Met-OH (0.1nM; 1h) enhanced the H2O2 release in macrophages pretreated with 25nM phorbol myristate acetate (PMA) [5]. Treatment with 12.5mg/ml Tyr-Gly-Gly-Phe-Met-OH for 48 hours significantly inhibited the proliferation of B16 cells and induced cell cycle arrest[6].
In vivo, Tyr-Gly-Gly-Phe-Met-OH treatment via intraperitoneal injection at a dose of 10mg/kg/day for 28 days significantly reduced the tumor volume in mice with the xenograft of MG-63 cells, without affecting body weight [7]. Tyr-Gly-Gly-Phe-Met-OH treatment (20mg/kg/day; i.p.) for 21 days inhibited tumor growth by enhancing the immunogenicity and recognition of MC38 cells in colorectal tumor-bearing mice and efficiently suppressed the mRNA expression of genes encoding inflammatory cytokines in the tumor tissues of mice [8].
References:
[1] Nagase H, Osa Y, Nemoto T, et al. Design and synthesis of novel delta opioid receptor agonists and their pharmacologies[J]. Bioorganic & medicinal chemistry letters, 2009, 19(10): 2792-2795.
[2]Zhao D, Plotnikoff N, Griffin N, et al. Methionine enkephalin, its role in immunoregulation and cancer therapy[J]. International immunopharmacology, 2016, 37: 59-64.
[3] Nabeshima T, Katoh A, Wada M, et al. Stress-induced changes in brain Met-enkephalin, Leu-enkephalin and dynorphin concentrations[J]. Life sciences, 1992, 51(3): 211-217.
[4] Kowalski J, Makowiecka K, Belowski D, et al. Augmenting effect of methionine-enkephalin on interleukin-6 production by cytokine-stimulated murine macrophages[J]. Neuropeptides, 2000, 34(3-4): 187-192.
[5] Stanojević S, Vujić V, Mitić K, et al. Methionine-enkephalin modulation of hydrogen peroxide (H2O2) release by rat peritoneal macrophages involves different types of opioid receptors[J]. Neuropeptides, 2008, 42(2): 147-158.
[6] Wang D M, Jiao X, Plotnikoff N P, et al. Killing effect of methionine enkephalin on melanoma in vivo and in vitro[J]. Oncology Reports, 2017, 38(4): 2132-2140.
[7] Huang H, Wang X, Zhang S, et al. In vitro and in vivo killing effects of methionine enkephalin on osteosarcoma[J]. International Immunopharmacology, 2023, 125: 111226.
[8] Wang X, Li S, Yan S, et al. Methionine enkephalin inhibits colorectal cancer by remodeling the immune status of the tumor microenvironment[J]. International Immunopharmacology, 2022, 111: 109125.
Tyr-Gly-Gly-Phe-Met-OH (Met-Enkephalin)是一种内源性阿片肽，作为δ阿片受体激动剂，EC50值为1.03nM[1]。Tyr-Gly-Gly-Phe-Met-OH可诱导巨噬细胞功能改变，刺激巨噬细胞的吞噬活性，并增强巨噬细胞产生细胞因子[2]。Tyr-Gly-Gly-Phe-Met-OH在小鼠模型中可作为应激诱导脑内变化的生物标志物[3]。
在体外，使用0.1nM的Tyr-Gly-Gly-Phe-Met-OH联合IFN-γ处理24小时，导致培养的小鼠巨噬细胞中IL-6的释放增加[4]。Tyr-Gly-Gly-Phe-Met-OH（0.1nM；1小时）增强了经25nM phorbol myristate acetate（PMA）预处理的巨噬细胞中H2O2的释放[5]。使用12.5mg/ml的Tyr-Gly-Gly-Phe-Met-OH处理48小时，显著抑制了B16细胞的增殖并诱导了细胞周期阻滞[6]。
在体内，每日腹腔注射10mg/kg剂量的Tyr-Gly-Gly-Phe-Met-OH，持续28天，显著降低了携带MG-63细胞异种移植瘤的小鼠的肿瘤体积，且未影响体重[7]。每日腹腔注射20mg/kg剂量的Tyr-Gly-Gly-Phe-Met-OH，持续21天，通过增强结直肠癌荷瘤小鼠中MC38细胞的免疫原性和识别能力来抑制肿瘤生长，并有效抑制了小鼠肿瘤组织中编码炎症细胞因子基因的mRNA表达[8]。