Photodynamic therapy reduced stemness and cell migration in triple-negative breast cancer cells through the PTEN/CD44 signaling pathway: A comparative study

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive, and the prognosis of affected patients is still unfavorable. Cancer stem cells have been highly implicated in tumor relapse and metastasis. Although zinc phthalocyanine (ZnPc) photodynamic therapy (PDT) has shown promising results in treating some cancers, the role of various PDT parameters on TNBC stemness remains unclear. In addition to performing in silico investigations, we evaluated the cytotoxic effects of ZnPc-PDT (8 and 24 J/cm²) on MDA-MB-468 cells using the MTT assay. We investigated its effects on apoptosis, cell cycle, and autophagy, and assessed stemness and migration via colony formation and scratch assays. Finally, we used qRT-PCR to determine mRNA expression levels of genes involved in apoptosis, migration, and stemness in cancer cells after the treatments. ZnPc-PDT (8 and 24 J/cm²) significantly decreased the cell viability, migration, and clonogenicity of MDA-MB-468 cells, while inducing apoptosis, autophagy, and sub-G1 arrest. These treatments upregulated the mRNA expression of Caspase-3 and Caspase-9. ZnPc-PDTs substantially downregulated the mRNA expression of BCL-2, MMP9, ROCK, IGF2, ALDH1A1, CD44, SOX2, CD133, and upregulated the mRNA expression of PTEN in MDA-MB-468 cells, specifically at ZnPc-PDT with 24 J/cm² energy density. ZnPc-PDT has shown promising results in reducing cancer development and stemness features in MDA-MB-468 cells, particularly at 24 J/cm². These results justify future preclinical and clinical studies to evaluate the potential of ZnPc-PDT to improve the prognosis and treatment of affected patients.

Keywords: MDA-MB-468 cell line; Photodynamic therapy; Stemness; Triple-negative breast cancer; Zinc phthalocyanine.