Chen Xingmeng, Chen Xi, Gao Junxiao, Yang Han, Duan Yue, Feng Yuxin, He Xin, Gong Xiaoqun, Wang Hanjie, Wu Xiaoli, Chang Jin
Tianjin Engineering Center of Micro Nano Biomaterials and Detection Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering, School of Life Sciences, Tianjin University, Tianjin, China.
College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Front Pharmacol. 2019 Aug 13;10:898. doi: 10.3389/fphar.2019.00898. eCollection 2019.
Natural killer (NK) cells play an irreplaceable role in the development of colon cancer, in which antitumor function of NK cells was impaired. Astragaloside III is a natural compound from Astragalus that has been shown to have immunomodulatory effects in various systems. However, few studies have evaluated the antitumor effects of Astragaloside III through stimulating systemic immunity and regulating NK cells. In this study, flow cytometry, immunohistochemical analysis, and immunofunctional assays were performed to elucidate the functions of Astragaloside III in restoring antitumor function of NK cells. We demonstrated that Astragaloside III significantly elevated the expression of natural killer group 2D (NKG2D), Fas, and interferon-γ (IFN-γ) production in NK cells, leading to increased tumor-killing ability. Experiments in cell co-culture assays and CT26-bearing mice model further confirmed that Astragaloside III could effectively impede tumor growth by increasing infiltration of NK cells into tumor and upregulating the antitumor response of NK cells. We further revealed that Astragaloside III increased IFN-γ secretion of NK cells by enhancing the expression of transcription factor T-bet. In conclusion, the effective anti-tumor function of Astragaloside III was achieved through up-regulation of the immune response of NK cells and elevation of NKG2D, Fas, and IFN-γ production.
自然杀伤(NK)细胞在结肠癌的发展中发挥着不可替代的作用,其中NK细胞的抗肿瘤功能受损。黄芪甲苷III是一种从黄芪中提取的天然化合物,已被证明在各种系统中具有免疫调节作用。然而,很少有研究通过刺激全身免疫和调节NK细胞来评估黄芪甲苷III的抗肿瘤作用。在本研究中,进行了流式细胞术、免疫组织化学分析和免疫功能测定,以阐明黄芪甲苷III在恢复NK细胞抗肿瘤功能中的作用。我们证明,黄芪甲苷III显著提高了NK细胞中自然杀伤细胞组2D(NKG2D)、Fas和干扰素-γ(IFN-γ)的表达,导致肿瘤杀伤能力增强。细胞共培养试验和荷CT26小鼠模型实验进一步证实,黄芪甲苷III可通过增加NK细胞向肿瘤的浸润和上调NK细胞的抗肿瘤反应来有效抑制肿瘤生长。我们进一步发现,黄芪甲苷III通过增强转录因子T-bet的表达来增加NK细胞的IFN-γ分泌。总之,黄芪甲苷III的有效抗肿瘤功能是通过上调NK细胞的免疫反应以及提高NKG2D、Fas和IFN-γ的产生来实现的。