Abstract
Photodynamic therapy (PDT) is a low-invasive method of treatment of various diseases, mainly neoplastic conditions. PDT has been experimentally combined with multiple treatment methods. In this study, we tested a combination of 5-aminolevulinic acid (5-ALA) mediated PDT with thalidomide (TMD), which is a drug presently used in the treatment of plasma cell myeloma. TMD and PDT share similar modes of action in neoplastic conditions. Using 4T1 murine breast carcinoma and 2H11 murine endothelial cells lines as an experimental tumor model, we tested 5-ALA-PDT and TMD combination in terms of cytotoxicity, apoptosis, Vascular Endothelial Growth Factor (VEGF) expression, and, in 2H11 cells, migration capabilities by wound healing assay. We have found an enhancement of cytotoxicity in 4T1 cells, whereas, in normal 2H11 cells, this effect was not statistically significant. The addition of TMD decreased the production of VEGF after PDT in 2H11 cell line. Our results reveal enhanced effectiveness of 5-ALA-PDT with TMD treatment compared to 5-ALA-PDT or TMD treatment alone. The addition of TMD may be a promising proceeding of the anti-tumor effect of PDT by decreasing the VEGF concentration in the culture medium. Further studies, including testing on different cell lines, are needed to confirm this assumption.
Highlights
Photodynamic therapy (PDT) is a minimally invasive procedure of treatment of different diseases, mainly cancers [1]
Our study aimed to investigate whether thalidomide enhances 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy in murine 4T1 breast cancer and 2H11 endothelial cell lines
The same dose of 5-ALA-PDT and thalidomide used for 2H11 cells presented very low phototoxicity and cytotoxicity, respectively
Summary
Photodynamic therapy (PDT) is a minimally invasive procedure of treatment of different diseases, mainly cancers [1]. Due to the irradiation of treated tissue with light at the proper wavelength, previously pre-excited by a delivered photosensitizing agent, it generates reactive oxygen species (ROS) [1]. After 4 h of incubation, increased production of protoporphyrin IX (PpIX) in tumor cells mitochondria is observed. Accumulated PpIX act as a photosensitizer in targeted cells. Excitation of the photosensitizer results in the formation of reactive oxygen species that exerts cytotoxic effects [2]. In the neoplastic process ROS generation results in the deterioration of cancerous tissue via several different manners [1]. The most apparent way is the induction of tumor cell apoptosis, autophagy and necrosis due to the damaging of external and internal lipid membranes and the release of caspase activators [1]. PDT influences vascular-endothelial growth factor (VEGF) expression and directly damages vessel wall, which results in the reduction
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