Mifespristone as a modulator of the multidrug resistant protein 1 on the blood brain barrier to increase the efficacy of doxorubicin on brain metastasis

RUBIN A, , , , , ; DE LA FUENTE V; CARABIAS P; TRONCOSO MF; LANARI C; ROJAS P

Congreso; Reunión Conjunta de Sociedades Biomédicas; 2017

The presence of multidrug resistance efflux transporters, such as the P-glycoprotein (P-gp) on the blood brain barrier (BBB), limits the efficacy of chemotherapeutic agents on brain tumors or metastases. The antiprogestin mifepristone (MFP) is known to inhibit P-gp activi- ty on tumor cells. We hypothesize that MFP treatment improves the efficacy of Pegylated doxorubicin liposomes (doxo) on brain tumors. We used the murine mammary carcinoma C4-2-HI whose growth is not inhibited by MFP treatment. Tumor cells (2x105) were injected into the brain of BALB/c-GFP mice using a stereotactic frame. Treatment with MFP (6 mg pellets, sc) and /or two weekly doses of doxo (4,5 mg/kg, iv) was initiated 10 days after cell inoculation. We analyzed the results by fluorescence microscopy, measuring the tumor volume on brain slices after DAPI staining. Confirming the hypothesis, a significant decrease in tumor size was only observed in mice treated with MFP and doxo (p