Department of Medicine, Division of Hematology and Oncology, Changhua Christian Hospital, Changhua 500, Taiwan.
Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, Taiwan.
Int J Mol Sci. 2022 Oct 24;23(21):12816. doi: 10.3390/ijms232112816.
Natural killer (NK) cell therapy is an emerging tool for cancer immunotherapy. NK cells are isolated from peripheral blood, and their number and activity are limited. Therefore, primary NK cells should be expanded substantially, and their proliferation and cytotoxicity must be enhanced. Shuterin is a phytochemical isolated from . In this study, we explored the possible capacity of shuterin to enhance the proliferation and activity of KHYG-1 cells (an NK leukemia cell line). Shuterin enhanced the proliferation of KHYG-1 cells and their cytotoxicity to K562 cells. Moreover, this phytochemical induced the expression of granzyme B by promoting the phosphorylated cyclic adenosine monophosphate response element-binding protein (CREB) and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, the secretion of interferon (IFN)-γ increased with increasing levels of shuterin in KHYG-1 cells and NK cells obtained from adults with head and neck squamous cell carcinoma. Shuterin appeared to induce IFN-γ secretion by increasing the expression of lectin-like transcript 1 and the phosphorylation of proteins involved in the Ras/Raf pathway. Thus, shuterin represents a promising agent for promoting the proliferation and cytotoxicity of NK cells.
自然杀伤 (NK) 细胞疗法是癌症免疫疗法的一种新兴工具。NK 细胞从外周血中分离出来，其数量和活性有限。因此，应该大量扩增原代 NK 细胞，并增强其增殖和细胞毒性。Shuterin 是一种从 中分离出来的植物化学物质。在这项研究中，我们探索了 Shuterin 增强 KHYG-1 细胞（一种 NK 白血病细胞系）增殖和活性的可能能力。Shuterin 增强了 KHYG-1 细胞的增殖及其对 K562 细胞的细胞毒性。此外，这种植物化学物质通过促进磷酸化环腺苷酸反应元件结合蛋白 (CREB) 和丝裂原激活蛋白激酶 (MAPK) 信号通路诱导颗粒酶 B 的表达。此外，随着 KHYG-1 细胞和来自头颈部鳞状细胞癌成人的 NK 细胞中 Shuterin 水平的增加，干扰素 (IFN)-γ 的分泌也增加。Shuterin 似乎通过增加凝集素样转录物 1 的表达和参与 Ras/Raf 途径的蛋白质磷酸化来诱导 IFN-γ 分泌。因此，Shuterin 是一种有前途的促进 NK 细胞增殖和细胞毒性的药物。
