Astragaloside III Enhances Anti-Tumor Response of NK Cells by Elevating NKG2D and IFN-γ.

Xingmeng Chen,Yue Duan,Xin He,Xiaoli Wu,Junxiao Gao,Yuxin Feng,Hanjie Wang,Jin Chang,Xi Chen,Xiaoqun Gong,Han Yang

doi:10.3389/fphar.2019.00898

Abstract

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.

Highlights

Colorectal cancer (CRC) is the second leading cause of cancer-related death and led to 0.55 million deaths in 2018 (Ferlay et al, 2015; Bray et al, 2018)
To investigate the effects of Astragaloside III on natural killer (NK) cells, the expressions of natural killer group 2D (NKG2D) and IFN-γ were examined in NK cells upon stimulation with Astragaloside III
The secretion of IFN-γ by NK cells isolated from spleen significantly increased in the treatment group than that in the control group (Figure S1), which indicated the direct activation of Astragaloside III on NK cells

Summary

Introduction

Colorectal cancer (CRC) is the second leading cause of cancer-related death and led to 0.55 million deaths in 2018 (Ferlay et al, 2015; Bray et al, 2018). Several conventional therapies are used for the treatment of CRC, the mortality rates of patients rank from 13% to 89% (Siegel et al, 2017), indicating the limitations of current treatments and urgent needs for more effective therapies. Among them, activating the function of innate immune cells-natural killer (NK) cells has been shown to exhibit strong anti-tumor effects (Hsu et al, 2018). NK cells are bone marrow-derived innate immune cells that play critical roles in the first line of defense against cancer (Pahl and Cerwenka, 2017).

Methods

Results

Conclusion