# Targeting NADPH oxidase 2 suppresses the growth of esophageal squamous cell carcinoma by regulating BTG2 pathway

## TL;DR

This study shows that reducing NOX2 in esophageal cancer cells slows their growth by increasing BTG2, suggesting NOX2 and BTG2 could be targets for treatment.

## Contribution

The study reveals a novel mechanism where NOX2 regulates BTG2 to influence esophageal squamous cell carcinoma progression.

## Key findings

- NOX2 deficiency reduced ESCC cell proliferation and induced apoptosis and G1 phase arrest.
- NOX2 knockdown increased BTG2 mRNA and protein expression in ESCC cell lines.
- High NOX2 expression correlated with poor prognosis, while high BTG2 expression indicated better outcomes in ESCC patients.

## Abstract

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) plays a carcinogenic role in various tumors. Recent study has reported that the carcinogenic mechanism of NOX2 in esophageal squamous cell carcinoma (ESCC) may be associated with the regulation of B-cell translocation gene 2 (BTG2). This study aims to clarify the role of NOX2 in the progression of ESCC.

NOX2 was knocked down in ESCC cell lines via siRNA transfection to assess its impact on cell function and BTG2 regulation. Tumor tissues from 66 ESCC patients were analyzed for NOX2 and BTG2 expression using immunohistochemistry to determine their clinical significance.

NOX2 deficiency inhibited ESCC cell proliferation, promoted apoptosis, and caused G1 phase arrest. Following NOX2 knockdown, BTG2 mRNA expression significantly increased in TE1 and KYSE30 cells, and a notable rise in BTG2 protein expression was observed in KYSE30 cells. Immunohistochemical analysis revealed that NOX2 expression was significantly higher in tumor tissues compared to adjacent non-cancerous tissues, while BTG2 expression was markedly lower in tumor tissues. High NOX2 expression correlated with poor prognosis, whereas high BTG2 expression indicated better outcomes. Multivariate analysis indicated that abnormal NOX2 and BTG2 expressions are independent prognostic factors for ESCC.

The carcinogenic role of NOX2 in ESCC may be associated with the regulation of BTG2 expression. The aberrant expressions of NOX2 and BTG2 are associated with the prognosis of patients with ESCC, suggesting that NOX2 and BTG2 could serve as potential biomarkers and therapeutic targets.

The online version contains supplementary material available at 10.1007/s12672-025-04345-7.