Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Int J Med Sci. 2017 Sep 19;14(12):1181-1188. doi: 10.7150/ijms.20661. eCollection 2017.
Upregulation of connexin 43 (Cx43) showed potential in enhancing immune surveillance that was suppressed in the tumor microenvironment. The expression of indoleamine 2, 3-dioxygenase (IDO) is one of the crucial factors contributing to tumor immune tolerance by depletion of tryptophan and IDO-mediated tryptophan metabolites. Here, we aim to investigate the role of Cx43 in IDO production in murine tumor by using Cx43 inducers. Resveratrol (trans-3, 5, 4 '-trihydroxystilbene) is a natural plant-derived polyphenol possessing positive effect against cancer. serovar choleraesuis (S.C.) was proved to target and inhibit tumor growth. Both of them regulated Cx43 expression in tumor cells and led to either chemosensitizing or immune-activating. In this study, the correlation between Cx43 and IDO were determined by the treatment of resveratrol and S.C. Our data showed an increase in Cx43 while IDO protein and IDO-mediated inhibited effects on T cell decreased after tumor cells are given with resveratrol and S.C.
All of which could be inhibited once the expression of Cx43 was blocked. Cx43 involved in IDO regulation might be useful in developing IDO-targeted cancer immune therapy.
细胞连接蛋白 43（Cx43）的上调显示出增强免疫监视的潜力，而免疫监视在肿瘤微环境中受到抑制。吲哚胺 2,3-双加氧酶（IDO）的表达是导致肿瘤免疫耐受的关键因素之一，它通过耗尽色氨酸和 IDO 介导的色氨酸代谢物来实现。在这里，我们旨在通过使用 Cx43 诱导剂来研究 Cx43 在小鼠肿瘤中 IDO 产生中的作用。白藜芦醇（反式-3,5,4 '-三羟基二苯乙烯）是一种天然植物来源的多酚，对癌症具有积极的作用。猪霍乱沙门氏菌（S.C.）被证明可以靶向并抑制肿瘤生长。它们都可以调节肿瘤细胞中的 Cx43 表达，从而导致化学增敏或免疫激活。在这项研究中，通过白藜芦醇和 S.C.的处理来确定 Cx43 与 IDO 之间的相关性。我们的数据显示，在用白藜芦醇和 S.C.处理后，Cx43 增加，而 IDO 蛋白和 IDO 介导的对 T 细胞的抑制作用降低。
一旦 Cx43 的表达被阻断，所有这些方法都可以被抑制。Cx43 参与 IDO 的调节可能有助于开发针对 IDO 的癌症免疫治疗。
