In vitro and In vivo 5-Aminolevulinic Acid-Based Photodynamic Therapy in Sensitive and Drug Resistant Leukemic Murine Cells

DIEZ B.,; HAJOS S.,; MEISS R.,; ERNST G.,; TEIJO MJ.,; BATLLE A.,; FUKUDA H.

Photodynamic Therapy: Fundamentals, Applications and Health Outcome Effects

Nova Science Publishers

Lugar: Hauppauge, NY ; Año: 2015; p. 173 - 191

ABSTRACT The effects of combined administration of doxorubicin (DOX) and vincristine (VCR), with 5- aminolevulinic acid photodynamic treatment (ALA-PDT), were analyzed in sensitive murine leukemic cell lines (LBR-) and DOX and VCR chemoresistant LBR-D160 and LBR-V160 cell lines. Low doses of DOX and VCR increased anti-cancer effect of ALA-PDT in LBR-cells. Decrease in cell survival was higher when the combination VCR + ALA-PDT was used compared to DOX + ALA-PDT. Resistant cell lines LBR-D160 and LBR-V160 were sensitive to ALA-PDT; however, no changes occured when combining therapies. Thus, ALA-PDT can overcome drug resistance and is a good candidate for using treating multidrug resistant (MDR) cells. This combined treatment were evaluated in a murine model . For this purpose, BALB/c mice were inoculated with LBR-cells previously treated with DOX or VCR plus ALA-PDT. 30 day after treatment animals were sacrificed and tumoral infiltration analyzed in many tissues: liver, kidney, spleen, lung, brain, timus, lymph nodes. Histologic studies revealed that in control animals inoculated with LBR-cells without any treatment, infiltration reached 87% in all the tissues analyzed. Animals inoculated with LBR-cells treated with only ALA-PDT, showed 50% of organs infiltrated. When animals were inoculated with cells treated with DOX or VCR, tumor infiltration were found in 87,5% and 75% of organs, respectively. In the case of inoculation with LBR- cells treated with DOX or VCR plus ALA-PDT, no evidence of tumor infiltration were observed in any of the tissues. These results show the beneficial effect of combining therapies, suggesting the potential therapeutic alternative in leukemic patients, additionaly bringing the possibility of diminishing chemotherapy dose, thus minimizing undesirable drug side effects.