Colegio de Farmaceuticos de la Provincia de Buenos Aires
Abstract
Multiple myeloma (MM) is a hematologic cancer characterized by the accumulation of malignant plasma cells. Bortezomib is the most effective chemotherapeutic drug used in treatment. However, drug resistance hinders efficient chemotherapy. One of the factors causing resistance is overexpression of multidrug-resistance genes. In this study, the expression of P-gp, MRP-1, MRP-2, MRP-3, MRP-6, MRP-7 and GSTP1 genes were investigated in MM cells. MTT assay was performed to determine bortezomib cytotoxicity in multiple myeloma KMS20 (bortezomib-resistant) and KMS28 (bortezomib-sensitive) cell lines. RNA isolation and cDNA synthesis were realized and the expressions of genes were analyzed by Realtime-qPCR. The results of the study suggest that P-gp is the main factor responsible for bortezomib resistance. MRP-1 expression appeared after P-gp expression reached a certain limit. This study is the first report indicating that MRP-7 is associated with bortezomib resistance in MM. Furthermore, the results demonstrated that bortezomib may be excreted from the cells by MRP-transporters after binding to glutathione with GSTP1. These findings will allow to develop new treatment strategies to prevent bortezomib resistance in MM
