School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
Chin J Integr Med. 2021 Jul;27(7):520-526. doi: 10.1007/s11655-020-3433-8. Epub 2020 Nov 10.
To investigate the effects of matrine on antigen presentation of dendritic cells (DCs), and to explore the pharmacological mechanism of matrine on anti-tumor effect.
Different concentrations (0, 1, 2, 4, 8 and 16 µ g/mL) of matrine were co-cultured with DCs, the harvested DCs were co-cultured with antigens of Lewis lung cancer (LLC) cells, and then DCs and T cells were co-cultured to produce DCs-activated killer (DAK) cells, which have significant tumor-killing activity. The expression of cytokines, mRNA and protein of toll-like receptors (TLRs) in DCs were detected by enzyme linked immunosobent assay, polymerase chain reaction and Western blot, respectively. And the killing effect of DAK were measured by MTT assay.
Matrine significantly increased the mRNA expression of TLR7, TLR8, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6) and I κ B kinase (IKK), as well as the protein expression of TLR7 and TLR8, and up-regulated the levels of interleukin-12 (IL-12), IL-6 and tumor necrosis factor-α (TNF-α), meanwhile, it also increased the expressions of MHC-II, CD54, CD80 and CD86 in DCs. DCs-activated effector T cells had significant tumor-killing activity. When the concentration of matrine was more than 4 µg/mL, all indices had significant difference (P<0.01 or P<0.05).
Matrine plays an anti-tumor role by regulating TLRs signal transduction pathway, promoting the secretion of inflammatory cytokines and enhancing immune function.
研究苦参碱对树突状细胞（DCs）抗原呈递的影响，探讨苦参碱抗瘤作用的药理学机制。
不同浓度（0、1、2、4、8 和 16 µg/mL）苦参碱与 DCs 共培养，收获的 DCs 与 Lewis 肺癌（LLC）细胞抗原共培养，然后将 DCs 和 T 细胞共培养产生具有显著肿瘤杀伤活性的 DC 激活杀伤（DAK）细胞。通过酶联免疫吸附试验、聚合酶链反应和 Western blot 分别检测 DCs 中细胞因子、Toll 样受体（TLRs）的 mRNA 和蛋白表达。并通过 MTT 法检测 DAK 的杀伤效应。
苦参碱显著增加 TLR7、TLR8、髓样分化因子 88（MyD88）、肿瘤坏死因子受体相关因子 6（TRAF-6）和 IκB 激酶（IKK）的 mRNA 表达，以及 TLR7 和 TLR8 的蛋白表达，上调白细胞介素-12（IL-12）、IL-6 和肿瘤坏死因子-α（TNF-α）水平，同时上调 DCs 中 MHC-II、CD54、CD80 和 CD86 的表达。DCs 激活效应 T 细胞具有显著的肿瘤杀伤活性。当苦参碱浓度大于 4 µg/mL 时，所有指标均有显著差异（P<0.01 或 P<0.05）。
苦参碱通过调节 TLRs 信号转导通路，促进炎症细胞因子的分泌，增强免疫功能，发挥抗肿瘤作用。
