Bahrami MohammadTaher, Haji Molla Hoseini Mostafa, Rezaei Mitra, Ziai Seyed Ali
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Evid Based Complement Alternat Med. 2021 Jul 13;2021:9927747. doi: 10.1155/2021/9927747. eCollection 2021.
Gastric adenocarcinoma is the fifth most diagnosed malignancy in the world. The immune system consists of a heterogeneous mixture of macrophages that defense the body through phagocytosis and the production of different cytokines and chemokines. Tumors cause macrophages to polarize differently in the manner of their favorite growth and angiogenesis. Umbelliprenin, a natural sesquiterpene coumarin, has been shown to have anticancer properties against some tumors, including gastric adenocarcinoma. The aim of our study was to investigate the effect of umbelliprenin on the polarization of macrophages in addition to the measurement of some of the soluble factors they produce.
The values of IC and IC for umbelliprenin in the AGS and THP-1 cells were estimated using the MTT assay. THP-1 cells were treated with 10 M umbelliprenin, either alone or cocultured with AGS cells. Flow cytometry analysis of treated THP-1 cells was performed for CD68, CD86, and CD206 markers to evaluate M0, M1, and M2 macrophages polarization, respectively. AGS cells were assessed for apoptosis and necrosis by flow cytometry after labeling with Annexin V-FITC and propidium iodide. Interleukin- (IL-) 10 and IL-12 contents were measured in the supernatant by the ELISA method. Griess Reaction assay technique was used to determine nitric oxide (NO) concentration.
The results of the MTT showed lower toxicity of umbelliprenin in THP-1 (IC = 75.79) compared to the AGS cell line (IC = 48.81). Umbelliprenin significantly increased the M1/M2 ratio. IL-10 content decreased significantly in the supernatant of M1 and M2 cells after umbelliprenin treatment, while IL-12 increased in the supernatant of M1 cells and decreased in the supernatant of the M2 cells. Umbelliprenin caused an increase in the NO in the supernatant of the M1 cells.
Umbelliprenin alters the macrophage's secretions and its phenotypes in favor of tumor suppression.
胃腺癌是全球第五大最常被诊断出的恶性肿瘤。免疫系统由巨噬细胞的异质混合物组成，这些巨噬细胞通过吞噬作用以及产生不同的细胞因子和趋化因子来保护身体。肿瘤会使巨噬细胞根据其偏好的生长和血管生成方式发生不同的极化。伞形前胡素是一种天然的倍半萜香豆素，已被证明对包括胃腺癌在内的一些肿瘤具有抗癌特性。我们研究的目的是除了测量巨噬细胞产生的一些可溶性因子外，还研究伞形前胡素对巨噬细胞极化的影响。
使用MTT法评估伞形前胡素在AGS和THP - 1细胞中的IC值和IC值。THP - 1细胞单独用10μM伞形前胡素处理，或与AGS细胞共培养。对处理后的THP - 1细胞进行流式细胞术分析，检测CD68、CD86和CD206标志物，分别评估M0、M1和M2巨噬细胞的极化情况。用膜联蛋白V - FITC和碘化丙啶标记后，通过流式细胞术评估AGS细胞的凋亡和坏死情况。采用ELISA法测定上清液中白细胞介素（IL）- 10和IL - 12的含量。采用Griess反应测定技术测定一氧化氮（NO）浓度。
MTT结果显示，与AGS细胞系（IC = 48.81）相比，伞形前胡素对THP - 1的毒性较低（IC = 75.79）。伞形前胡素显著提高了M1/M2比值。伞形前胡素处理后，M1和M2细胞上清液中的IL - 10含量显著降低，而M1细胞上清液中的IL - 12增加，M2细胞上清液中的IL - 12减少。伞形前胡素使M1细胞上清液中的NO增加。
伞形前胡素改变巨噬细胞的分泌及其表型，有利于肿瘤抑制。
