Department of Biomedical Science, Kyungpook National University, Daegu, 41566, South Korea.
Department of Biomedical Science, Kyungpook National University, Daegu, 41566, South Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, South Korea; Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, 41566, South Korea.
Biochem Biophys Res Commun. 2024 Jun 4;711:149921. doi: 10.1016/j.bbrc.2024.149921. Epub 2024 Apr 9.
Artificial sweeteners, which contain no or few calories, have been widely used in various foods and beverages, and are regarded as safe alternatives to sugar by the Food and Drug Administration. While several studies suggest that artificial sweeteners are not related to cancer development, some research has reported their potential association with the risk of cancers, including hepatocellular carcinoma (HCC). Here, we investigated whether acesulfame potassium (Ace K), a commonly used artificial sweetener, induces immune evasion of HCC cells by upregulating programmed death ligand-1 (PD-L1). Ace K elevated the protein levels of PD-L1 in HCC cells without increasing its mRNA levels. The upregulation of PD-L1 protein levels in HCC cells by Ace K was induced by attenuated autophagic degradation of PD-L1, which was mediated by the Ace K-stimulated ERK1/2-mTORC1 signaling pathway. Ace K-induced upregulation of PD-L1 attenuated T cell-mediated death of HCC cells, thereby promoting immune evasion of HCC cells. In summary, the present study suggests that Ace K promotes HCC progression by upregulating the PD-L1 protein level.
人工甜味剂不含热量或仅含少量热量，已广泛应用于各种食品和饮料中，被美国食品药品监督管理局（FDA）视为糖的安全替代品。虽然有几项研究表明人工甜味剂与癌症发展无关，但一些研究报告称它们可能与某些癌症（包括肝细胞癌（HCC））的风险有关。在这里，我们研究了常用人工甜味剂乙酰磺胺酸钾（Ace K）是否通过上调程序性死亡配体-1（PD-L1）来诱导 HCC 细胞的免疫逃逸。Ace K 在不增加其 mRNA 水平的情况下，上调 HCC 细胞中 PD-L1 的蛋白水平。Ace K 通过抑制 PD-L1 的自噬降解，激活 ERK1/2-mTORC1 信号通路，诱导 HCC 细胞中 PD-L1 蛋白水平的上调。Ace K 诱导的 PD-L1 上调减弱了 T 细胞介导的 HCC 细胞死亡，从而促进了 HCC 细胞的免疫逃逸。总之，本研究表明 Ace K 通过上调 PD-L1 蛋白水平促进 HCC 进展。
