Photodynamic Inactivation with Acridine Orange on a Multidrug‐resistant Mouse Osteosarcoma Cell Line

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Abstract
Overcoming multidrug resistance (MDR) is an urgent issue to improve the prognosis of osteosarcoma patients. In this study, we undertook to clarify the effect of photodynamic therapy (PDT) with acridine orange (AO) on the MDR mouse osteosarcoma (MOS/ADR1) cell line, by comparing the outcome with the effect on a chemosensitive osteosarcoma (MOS) cell line. Cultured cells of MOS and MOS/ADR1 cell lines were exposed to AO at various concentrations for various times, followed by long‐ or short‐term (10 or 1 min) illumination with blue light (466.5 nm) for excitation. Living cells were counted by means of the trypan blue exclusion test. The results showed that AO rapidly bound to DNA, RNA and lysosomes of living MOS and MOS/ADR1 cells and also that most tumor cells in both cell lines died rapidly (viability ratio to untreated cells: 1/1000) within 48 h under conditions of continuous or 15‐min flash exposure to AO at concentrations above 1.0 μg/ ml plus 10‐min illumination with blue light. Even after flash exposure to AO at concentrations above 1.0 μg/ml plus 1‐min illumination, the viability of MOS/ADR1 cells decreased to a viability ratio of less than 1/1000 within 72 h. Based on these results, we concluded that AO with photo excitation has a strong cytocidal effect, not only on chemosensitive mouse osteosarcoma cells, but also on MDR mouse osteosarcoma cells. These results suggested that photodynamic therapy with AO may be a new approach to treating MDR human osteosarcomas.