Background: Treatment for triple-negative breast cancer (TNBC) remains a significant challenge due to a lack of targeted therapies. While photodynamic therapy (PDT) has been utilized as a treatment approach for several types of cancer, oxyphotodynamic therapy (OPDT) is a novel method that improves treatment efficacy by increasing local oxygen concentration. Metformin (MET) has been demonstrated utility as an anti-tumor agent by acting through the adenosine monophosphate-activated protein kinase (AMPK) pathway. We hypothesized that MET in combination with heme, a byproduct of 5-aminolevulinic acid (ALA), may increase cytotoxicity for cancer treatment. This study aimed to investigate the synergistic effect of MET and ALA with PDT or OPDT on TNBC tumorigenic cells.
Methods:The treatment efficacy and phototoxicity of PDT or OPDT were determined using a cell viability assay. PDT/OPDT experiments were carried out in nine groups based on different combinations and concentrations of ALA and/or MET. To calculate the synergistic effect by compuSyn soft for different groups, cells were incubated with ALA and/or MET at the following concentrations (0, 0.25, 0.5,1, 2, 4, 8, 16, 24, and 32 mM). The fluorescence of ALA-induced protoporphyrin IX (PpIX) and MitoTracker Green were observed under a confocal microscope.