Park Arum, Yang Yunjeong, Lee Yunhee, Jung Haiyoung, Kim Tae-Don, Noh Ji-Yoon, Lee Seungjin, Yoon Suk Ran
Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
Department of Pharmacology, College of Pharmacy, Chungnam University, Daejeon, South Korea.
Front Med (Lausanne). 2022 Aug 18;9:973681. doi: 10.3389/fmed.2022.973681. eCollection 2022.
(AFI), extensively used in traditional herbal medicine, is known to have diverse physiological effects against various diseases, including obesity, diabetes, and cardiovascular disease. However, the effects of AFI on the immune system, especially natural killer (NK) cells, remain largely unknown. We aimed to investigate the effect of AFI on NK cell activity and and to elucidate the underlying mechanisms. Further, we verified the anticancer efficacy of AFI in a mouse lung metastasis model, underscoring the therapeutic potential of AFI in cancer therapy. Our results revealed that AFI significantly enhanced the cytolytic activity of NK cells in a dose-dependent manner, accompanied by an increase in the expression of NK cell-activating receptors, especially NKp30 and NKp46. AFI treatment also increased the expression of cytolytic granules, including granzyme B and perforin. Furthermore, the expression of CD107a, a degranulation marker, was increased upon treatment with AFI. A signaling study using western blot analysis demonstrated that the phosphorylation of extracellular signal-regulated kinase (ERK) was involved in increasing the NK cell activity following AFI treatment. In the study performed in mice, oral administration of AFI markedly enhanced the cytotoxic activity of spleen mononuclear cells against YAC-1 cells, which was accompanied by NKp46 upregulation. In addition, we confirmed that cancer metastasis was inhibited in a mouse cancer metastasis model, established using the mouse melanoma B16F10 cell line, by the administration of AFI Collectively, these results indicate that AFI enhances NK cell-mediated cytotoxicity and activation of the ERK signaling pathway and suggest that AFI could be a potential supplement for cancer immunotherapy.
非洲楝（AFI）广泛应用于传统草药医学，已知其对包括肥胖症、糖尿病和心血管疾病在内的多种疾病具有多种生理作用。然而，AFI对免疫系统，尤其是自然杀伤（NK）细胞的影响在很大程度上仍不清楚。我们旨在研究AFI对NK细胞活性的影响，并阐明其潜在机制。此外，我们在小鼠肺转移模型中验证了AFI的抗癌疗效，强调了AFI在癌症治疗中的治疗潜力。我们的结果显示，AFI以剂量依赖的方式显著增强了NK细胞的细胞溶解活性，同时NK细胞激活受体，尤其是NKp30和NKp46的表达增加。AFI处理还增加了包括颗粒酶B和穿孔素在内的细胞溶解颗粒的表达。此外，用AFI处理后，脱颗粒标志物CD107a的表达增加。使用蛋白质印迹分析进行的信号研究表明，细胞外信号调节激酶（ERK）的磷酸化参与了AFI处理后NK细胞活性的增加。在对小鼠进行的研究中，口服AFI显著增强了脾单核细胞对YAC-1细胞的细胞毒性活性，同时伴有NKp46上调。此外，我们证实，在使用小鼠黑色素瘤B16F10细胞系建立的小鼠癌症转移模型中，给予AFI可抑制癌症转移。总体而言，这些结果表明，AFI增强了NK细胞介导的细胞毒性以及ERK信号通路的激活，并表明AFI可能是癌症免疫治疗的一种潜在补充剂。
