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

Farhad Jeddi1, Narges Soozangar1, Mohammad Reza Sadeghi2

  • 1Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|November 2, 2017
PubMed

Insights

Multidrug resistance in gastric cancer (GC) is linked to elevated Nrf2 (nuclear factor erythroid 2-related factor 2) and P-gp (P-glycoprotein) expression. Inhibiting Nrf2 may improve chemotherapy effectiveness in GC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Gastric cancer (GC) exhibits poor chemotherapeutic efficacy due to multidrug resistance (MDR).
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates detoxifying enzymes and efflux transporters like P-glycoprotein (P-gp).
  • Understanding the Nrf2-P-gp association in GC is crucial for improving treatment outcomes.

Purpose of the Study:

  • To investigate the association between Nrf2 and P-gp expression in gastric cancer.
  • To correlate Nrf2 and P-gp levels with clinicopathological features in GC patients.

Main Methods:

  • Real-time PCR and immunohistochemical staining (IHC) were used to assess Nrf2 and MDR1/P-gp mRNA and protein levels.
  • Samples from 60 GC patients and non-GC individuals were analyzed.
  • Statistical analyses included Mann-Whitney test, correlation analysis (r), and Chi-square test.

Main Results:

  • Nrf2 expression was significantly higher in GC patients (46.7%) compared to non-GC individuals (11.7%) (p<0.001).
  • P-gp induction was associated with Nrf2 overexpression (r=0.55, p<0.001).
  • Nrf2 overexpression correlated with tumor size, histological grade, lymph node, and distant metastasis; P-gp upregulation correlated with histological grade and tumor size.

Conclusions:

  • Nrf2 plays a significant role in gastric cancer development and multidrug resistance.
  • Therapeutic inhibition of Nrf2 could potentially enhance chemotherapy efficacy in GC by downregulating P-gp.
Keywords:
ChemotherapyClinicopathological criteriaGastric cancerMDR1/P-gpNrf2

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