5th World Congress on Cancer Therapy
Royal College of Surgeons in Ireland, Ireland
Title: Inhibition of multidrug resistance protein I (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme
Biography: Tivnan A
Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with an 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%, with delivery across the blood brain barrier (BBB) or chemoresistance contributing to the extremely poor outcomes despite treatment. Increased expression of the multidrug resistance protein 1(MRP1) in high grade glioma, and it’s role in BBB active transport, highlights this member of the ABC transporter family as a target for improving drug responses in GBM. In this study we show that small molecule inhibitors, and gene silencing, of MRP1 had a signifi cant eff ect on GBM cell response to Temozolomide (150μM), Vincristine (100nM) and Etoposide (2μM). Pre-treatment with Reversan (inhibitor of MRP1 and P-glycoprotein) led to a signifi cantly improved response to cell death in the presence of all three chemotherapeutics, in both primary and recurrent GBM cells. Th e presence of MK571 (inhibitor of MRP1 and Multidrug resistance protein 4(MRP4) led to an enhanced eff ect of Vincristine and Etoposide in reducing cell viability over a 72 hour period. Specifi c MRP1 inhibition led to a signifi cant increase in Vincristine and Etoposide-induced cell death in all three cell lines assessed. Treatment with MK571, or specifi c MRP1 knockdown, did not have any eff ect on Temozolomide drug response in these cells. Th ese fi ndings have signifi cant implications in providing researchers an opportunity to improve currently used chemotherapeutics for the initial treatment of primary GBM, and improved treatment for recurrent GBM patients. Th is work is funded by Irish Cancer Society Research Fellowship CRF13TIV, supported by Tesco Charity of the Year.