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NF-κB–Associated Inflammatory Injury in Lung Cancer Cells: Evaluation in Syngeneic Mouse Models

Andrei-Mihai Popescu, MD, PhD1  ORCID

1 Department of Oncology and Molecular Biology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Romania

DOI: 10.18081/2378-5225/14.97  
Cited by 0

 Article history: Received 27 February 2024 · Revised 11 March 2025 · Accepted 19 April 2025 · Published 01 May 2025

© 2025 Popescu. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0). 

CC BY 4.0                                                                                                   

Abstract

Background: Nuclear factor kappa B (NF-κB) is a key transcription factor linking inflammation to cancer progression and cellular injury. In lung cancer, persistent NF-κB activation contributes to tumor growth, inflammatory cytokine production, and oxidative stress; however, its precise role in mediating inflammation-associated cellular injury within an intact immune microenvironment remains incompletely understood.

Objective: To investigate the role of NF-κB–associated inflammatory signaling in inducing cellular injury and tumor progression in lung cancer using a syngeneic murine model.

Methods: A controlled experimental study was conducted using Lewis lung carcinoma (LLC1) cells implanted in C57BL/6 mice (n = 48). Animals were randomized into four groups: control, NF-κB activation (lipopolysaccharide, LPS), NF-κB inhibition (BAY 11-7082), and combination treatment. Tumor growth was monitored over 28 days. NF-κB activation was assessed by Western blot and immunohistochemistry. Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were quantified using ELISA and qRT-PCR. Oxidative stress markers (ROS, MDA, GSH, LDH) and histopathological changes were evaluated. Flow cytometry was performed to analyze immune cell infiltration and apoptosis. Statistical analysis was conducted using one-way ANOVA with post hoc testing.

Results: NF-κB activation significantly increased tumor volume (2,180 ± 240 mm³ vs 1,420 ± 180 mm³ in controls, p < 0.01), accompanied by elevated phosphorylation of NF-κB p65 and degradation of IκB-α. LPS-treated tumors exhibited marked upregulation of TNF-α, IL-6, and IL-1β (p < 0.001), increased oxidative stress (ROS and MDA), and reduced antioxidant capacity (GSH). Histological analysis revealed extensive necrosis and inflammatory infiltration. In contrast, NF-κB inhibition with BAY 11-7082 significantly reduced tumor growth (820 ± 130 mm³, p < 0.01), suppressed cytokine production, restored redox balance, and increased apoptosis (Annexin V⁺ cells: 32% ± 4%). Flow cytometry demonstrated decreased macrophage infiltration and enhanced CD8⁺ T-cell responses following NF-κB inhibition.

Conclusions: NF-κB activation promotes inflammation-driven cellular injury, oxidative stress, and tumor progression in lung cancer, while its inhibition exerts protective and anti-tumor effects. Targeting NF-κB–associated inflammatory pathways represents a promising therapeutic strategy; however, selective modulation is required to preserve physiological immune function.

Keywords: NF-κB; lung cancer; cellular injury; inflammation; oxidative stress; cytokines; syngeneic mouse model

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BM-Publisher · Pathophysiology of Cell Injury Journal (PCIJ) · E-ISSN 2378-5225 · DOI Prefix 10.18081/pcij/2378-5225

Pathophysiology of Cell Injury Journal (PCIJ)
E-ISSN 2378-5225 · Biannual
BM-Publisher (London, UK)
Open Access

Vol 14, Issue 1 (June 2025), pp. 76–97

How to cite (AMA)

Popescu AM. NF-κB–Associated Inflammatory Injury in Lung Cancer Cells: Evaluation in Syngeneic Mouse Models. Pathophysiology of Cell Injury Journal (PCIJ). 2025;14(1):76–97. doi: 10.18081/2378-5225/14.97.

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