The Impact of Nrf2 Silencing on Nrf2-PD-L1 Axis to Overcome Oxaliplatin Resistance  and Migration in Colon Cancer Cells

Zahra Payandeh; Abbas  Pirpour Tazehkand; Behzad Mansoori; Vahid Khaze; Milad Asadi; Behzad Baradaran; Nasser Samadi

doi:10.18502/ajmb.v13i3.6371

Zahra Payandeh Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Abbas Pirpour Tazehkand Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences,Tabriz, Iran
Behzad Mansoori Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Vahid Khaze Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Milad Asadi Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Behzad Baradaran Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Nasser Samadi Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences,Tabriz, Iran

DOI: https://doi.org/10.18502/ajmb.v13i3.6371

Keywords: Colonic neoplasms, Humans, NF-E2-Related Factor 2, Oxaliplatin, Signal transduction

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.