Electric Field-Based Cancer Therapy Induces the Expression of HMGB1 and PD-L1 mRNA Genes on Breast Tumor of Female Rats

The study observed that exposing breast tumor samples in rats to electric fields led to increased activity in specific genes, potentially influencing the tumor’s behavior. Additionally, it demonstrated the safety of ECCT for healthy organs, particularly the brain and liver, in female rats.

Key Findings

1. Up-Regulation of HMGB1 and PD-L1 in Breast Tumor Tissue: Significant up-regulation of HMGB1 mRNA in the therapy (IT) group compared to the non-therapy (INT) group. Significant up-regulation of PD-L1 mRNA in the IT group, indicating enhanced expression following ECCT exposure. Amplification and melt peak curves confirmed the specificity of the primers used for both genes.
2. No Significant Changes in Brain and Liver Tissues: No significant changes in the expression of HMGB1 and PD-L1 in healthy brain tissues after ECCT exposure. No significant changes in the expression of HMGB1, PD-L1, and interferon-γ in healthy liver tissues post-ECCT exposure.
3. Tumor Microenvironment Impact: ECCT may affect tumor interstitial fluid (TIF) formation, influencing the tumor microenvironment. This disruption can impair the ability of cancer cells to sustain themselves, contributing to tumor shrinkage.
4. Safety and Efficacy: Histopathological observations showed no damage in non-tumor tissues, underscoring the safety of ECCT. This therapy selectively targets cancer cells without affecting normal cells, a crucial advantage over conventional therapies. The absence of histopathological changes in non-tumor tissues reinforces the safety of ECCT, ensuring effective treatment without significant side effects.
5. Modulation of Cellular Proliferation and Apoptosis: Significant up-regulation of HMGB1 in the IT group suggests that ECCT promotes immunogenic cell death (ICD), enhancing the immune response against tumors. PD-L1 up-regulation in the IT group, along with increased CD8+ T cell activity, indicates an anti-tumor immune response rather than immune suppression.
6. Down-Regulation of Inflammatory Cytokines in Tumor Tissue: Significant down-regulation of CCL2 and IL18 in the IT group indicates that ECCT reduces pro-inflammatory and pro-tumorigenic signals. CCL2 is involved in recruiting monocytes and macrophages to the tumor site, while IL18 promotes cell proliferation and migration. Their reduction suggests a less favorable environment for tumor growth and metastasis.