Payandeh Zahra, Pirpour Tazehkand Abbas, Mansoori Behzad, Khaze Vahid, Asadi Milad, Baradaran Behzad, Samadi Nasser
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Avicenna J Med Biotechnol. 2021 Jul-Sep;13(3):116-122. doi: 10.18502/ajmb.v13i3.6371.
Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a key role in promoting chemoresistance in various cancers. PD-L1 is one of the downstream targets of the Nrf2 signaling pathway. This molecule has some beneficial impacts on tumors growth by inhibition of the immune system. This study aimed to investigate the potential role of the Nrf2-PD-L1 axis in the promotion of oxaliplatin resistance in colon cancer cells.
We examined Nrf2, PD- L1, and CD80 expression in the tumor and margin tissue samples from CRC patients. After that role of the Nrf2-PD-L1 axis in promotion of Oxaliplatin resistance was investigated.
Our data revealed that Nrf2 and PD-L1 mRNA expressions were markedly higher in tumor tissues compared to margin tissues. The PD-L1 mRNA expression level was also increased in the resistant cells. However, Nrf2 expression was decreased in SW480/Res cells and increased in LS174T/Res cells. The inhibition of Nrf2 through siRNA treatment in SW480/Res and LS174T/Res cells has decreased the IC50 values of oxaliplatin. Inhibition of the Nrf2 has significantly increased the oxaliplatin-induced apoptosis, and reduced the migration in SW480/Res cells.
It is suggested that effective inhibition of Nrf2-PD-L1 signaling pathways can be considered as a novel approach to improve oxaliplatin efficacy in colon cancer patients.
核因子红细胞2相关因子2（Nrf2）在促进多种癌症的化疗耐药性中起关键作用。程序性死亡受体配体1（PD-L1）是Nrf2信号通路的下游靶点之一。该分子通过抑制免疫系统对肿瘤生长有一些有益影响。本研究旨在探讨Nrf2-PD-L1轴在促进结肠癌细胞奥沙利铂耐药性中的潜在作用。
我们检测了结肠癌患者肿瘤及切缘组织样本中Nrf2、PD-L1和CD80的表达。此后研究了Nrf2-PD-L1轴在促进奥沙利铂耐药性中的作用。
我们的数据显示，与切缘组织相比，肿瘤组织中Nrf2和PD-L1 mRNA表达明显更高。耐药细胞中PD-L1 mRNA表达水平也升高。然而，Nrf2在SW480/Res细胞中表达降低，在LS174T/Res细胞中表达升高。通过小干扰RNA（siRNA）处理在SW480/Res和LS174T/Res细胞中抑制Nrf2可降低奥沙利铂的半数抑制浓度（IC50）值。抑制Nrf2可显著增加奥沙利铂诱导的细胞凋亡，并减少SW480/Res细胞的迁移。
提示有效抑制Nrf2-PD-L1信号通路可被视为提高结肠癌患者奥沙利铂疗效的一种新方法。
