Down-modulation of MDR1 function enhances TH9402-mediated cytotoxicity.

(A) Resting PBMCs were exposed to 10 μM TH9402 in medium supplemented or not with verapamil. Elimination of CD4⁺ and CD8⁺ cell populations was measured 3 days after PDCT using flow cytometry and compared with untreated controls. Inhibition ofMDR1 function increased the photodynamic elimination of T cells. (B) Cytotoxicity of PDCT on KG1a cells, anMDR1-expressing cell line, was measured using an LDA. Verapamil alone or PDCT with 5 μM TH9402 had no effect on KG1a cells but combining the inhibition of MDR1 with verapamil to TH9402 PDCT resulted in the elimination of more than 3 logs of clonogenic cells. Results are expressed as mean ± SEM of at least 2 experiments.