Therapeutic effects of systemic photodynamic therapy in a leukemia animal model using A20 cells

Abstract

Photodynamic therapy (PDT) is attracting attention because of its noticeable inhibitory effects on the growth of dermatological and other solid tumors. Here, we studied the use of PDT in systemic diseases such as leukemia, lymphoma, and metastatic cancer, for which tumor formation areas cannot be clearly compartmentalized. We developed a systemic PDT method and examined its effect in a leukemia mouse model. Growth inhibition of A20 cells (H-2(d), murine B-lymphoma/leukemia, and Balb/c origin) induced by PDT/Photodithazine was evaluated by EZ-Cytox assay. After PDT, changes in cell morphology were assessed by light microscopy. Induction of apoptosis, as well as changes in the cell cycle, were assessed by fluorescence-activated cell sorting (FACS) analysis. A20 cells were injected into Balb/c mice through the tail veins, and PDT was performed. A total of 10 mg kg(-1) body weight of Photodithazine concentration was injected intravenously. After 5 min, micro photofibers (diameter, 200 μm) were inserted into the tail veins and irradiated at 1,200 J with a laser. PDT inhibited growth of A20 cells and resulted in marked morphological changes. PDT also induced apoptosis and G1 arrest. In a leukemia mouse model, systemic PDT increased the survival rate (p < 0.01). This is the first report of the effects of systemic PDT in a leukemia animal model. PDT has been applied only locally in most cases, for example to solid tumors. This study provides experimental evidence that systemic PDT could effectively be applied to systemic and spread tumors, for which tumor formation areas cannot clearly be determined.