Inhibition of multidrug resistance protein 1 (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme.

摘要: Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with extremely poor prognostic outcome despite intensive treatment. All chemotherapeutic agents currently used have no greater than 30-40% response rate, many fall into the range of 10-20%, delivery across blood barrier (BBB) or chemoresistance contributing to outcomes Increased expression multidrug resistance protein 1(MRP1) in high grade glioma, and it’s role BBB active transport, highlights this member ABC transporter family as target for improving drug responses GBM. In study we show that small molecule inhibitors gene silencing MRP1 had significant effect on GBM cell temozolomide (150µM), vincristine (100nM) etoposide (2µM). Pre-treatment Reversan (inhibitor P-glycoprotein) led significantly improved death presence all three chemotherapeutics, both primary recurrent cells. The MK571 Multidrug 4 (MRP4) an enhanced reducing viability over 72 hour period. Specific inhibition increase etoposide-induced lines assessed. Treatment MK571, specific knockdown, did not any these These findings implications providing researchers opportunity improve chemotherapeutics initial treatment GBM, patients.