Resistance to Photodynamic Therapy in Murine Leukemia Cells In Vitro

抄録

A photodynamic therapy (PDT)-resistant variant of the P388 murine leukemia cell line was isolated by repeated PDT with mono-L-aspartyl chlorin e6 (NPe 6) in vitro to the 0.1% survival level, followed by twelve regrowth cycles. The resistant variant was 1.38-fold more resistant to PDT with NPe 6 (10-15 μg/ml). However, more than 20 μg/ml, there was no difference between cells. The PDT-12 cells had less uptake of NPe 6 after 2h incubation than P388. We examined cross-resistance to adriamycin and the partitioning behavior determinant of the aqueous biphasic system. There was no difference in cytotoxicity and the uptake of adriamycin (ADM) between parental and PDT-12 cells. Partitioning behavior of parental cells and PDT-12 cells was compared. The latter has an inherently higher degree of membrane hydrophobicity. NPe 6 is comparatively hydrophilic, but the P388/ADR cells had reduced accumulation of the drug by extrusion by P-glycoprotein rather than membrane hydrophobicity. Furthermore, NPe 6-PDT cytotoxicity depended on accumulation into cells. Therefore, the PDT-12 cells acquired a hydrophobic membrane by repeating NPe 6-PDT twelve times. The PDT-12 cells were not cross-resistant to adriamycin. NPe 6 penetration into PDT-12cells was prevented by membrane hydrophobicity.