Nrf2 overexpression is associated with P-glycoprotein upregulation in gastric cancer

Publication date: January 2018 Source:Biomedicine & Pharmacotherapy, Volume 97 Author(s): Farhad Jeddi, Narges Soozangar, Mohammad Reza Sadeghi, Mohammad Hossein Somi, Masoud Shirmohamadi, Amir-Taher Eftekhar-Sadat, Nasser Samadi The efficacy of chemotherapeutic agents remains very poor in gastric cancer (GC) patients due to the development of multidrug resistance (MDR) phenotype. The nuclear factor erythroid 2-related factor 2 (Nrf2), is a pivotal transcriptional factor that regulates phase II detoxifying enzymes, antioxidants and efflux transporters including P-glycoprotein (P-gp). The aim of this study was to investigate the association of Nrf2 and P-gp and their correlations with clinicopathological criteria in GC patients.Nrf2 and MDR1/P-gp expressions in both mRNA and protein levels were examined by real-time PCR and immunohistochemical staining (IHC) respectively, in endoscopic biopsy samples from60 GC patients compared with those expressions in non-GC individuals. Our results from IHC examinations revealed that Nrf2 expression in GC patients (46.7%) is markedly higher than that in non-GC individuals (11.7%) (p <0.001, Mann–Whitney test) which was confirmed by real-time PCR in mRNA levels. Induction of P-gp as a drug efflux pump, was associated with Nrf2 overexpression in these samples (r =0.55, p< 0.001). There was also a strong correlation between Nrf2 overexpression and tumor size, histological grade, lymph node and distant metastasi...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research