AbstractBackground and ObjectivesPhotodynamic therapy (PDT) has been proposed as an alternative approach in overcoming multidrug resistance (MDR) phenotype. To verify whether 5‐aminolevulinic acid (ALA)‐mediated PDT is effective in MDR cells, we studied the protoporphyrin IX (PpIX) content, intracellular localization, and phototoxicity in human breast cancer cells MCF‐7 and derived MDR subline, MCF‐7/ADR.Study Design/Materials and MethodsThe fluorescence kinetics of ALA‐induced PpIX was evaluated by spectrofluorometer. The phototoxicity of MCF‐7 and MCF‐7/ADR cells was determined by tetrazolium (MTT) assays and clonogenic assay. Furthermore, Annexin V and propidium iodide (PI) binding assays were performed to analyze the characteristics of cell death after ALA–PDT.ResultsMCF‐7/ADR accumulated a lower level of PpIX as compared to parental MCF‐7 cells. Significant phototoxicity was observed in MCF‐7 and increased in a fluence‐dependent manner with LD50 around 8 J/cm2. Compared to its parental counterpart, MCF‐7/ADR cells were less sensitive to ALA photodynamic treatment and PDT‐induced cytotoxicity did not increase in a dose responsive manner as the concentration of ALA increased or the fluence of light increased. ALA–PDT was less effective for MCF‐7/ADR cells than MCF‐7 cells even under the condition when these two cell lines contained the similar amounts of PpIX.ConclusionsThese results indicate that, except for the MDR related characteristics, MCF‐7/ADR cells might possess intrinsic mechanisms that render them less sensitive to ALA–PDT induced phototoxicity. Lasers Surg. Med. 34:62–72, 2004. © 2004 Wiley‐Liss, Inc.