MIFEPRISTONE AS A MODULATOR OF THE MULTIDRUG RESISTANT PROTEIN 1 ON THE BLOOD BRAIN BARRIER TO INCREASE THE EFFICACY OF DOXORUBICIN ON BRAIN METASTASES

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

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

The presence of multidrug resistance efflux transporters, such asthe P-glycoprotein (P-gp) on the blood brain barrier (BBB), limits theefficacy of chemotherapeutic agents on brain tumors or metastases.The antiprogestin mifepristone (MFP) is known to inhibit P-gp activityon tumor cells. We hypothesize that MFP treatment improves theefficacy of Pegylated doxorubicin liposomes (doxo) on brain tumors.We used the murine mammary carcinoma C4-2-HI whose growth isnot inhibited by MFP treatment. Tumor cells (2x105) were injectedinto the brain of BALB/c-GFP mice using a stereotactic frame.Treatment with MFP (6 mg pellets, sc) and /or two weekly dosesof doxo (4,5 mg/kg, iv) was initiated 10 days after cell inoculation.We analyzed the results by fluorescence microscopy, measuring thetumor volume on brain slices after DAPI staining. Confirming thehypothesis, a significant decrease in tumor size was only observedin mice treated with MFP and doxo (p