Effect of magnetic nanoparticles of Fe3O4 and 5-bromotetrandrine on reversal of multidrug resistance in K562/A02 leukemic cells

Abstract

Jian Cheng1*, Weiwei Wu1*, Bao-an Chen1, Feng Gao1, Wenlin Xu2, Chong Gao1, Jiahua Ding1, Yunyu Sun1, Huihui Song1, Wen Bao1, Xinchen Sun3, Cuirong Xu1, Wenji Chen1, Ningna Chen1, Lijie Liu4, Guohua Xia1, Xiaomao Li5, Xuemei Wang61Department of Hematology, 3Department of Oncology, The Afiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China; 2Department of Hematology, The First People’s Hospital of Zhengjiang, Zhenjiang, People’s Republic of China; 4Institution of Physiology, 6State Key Lab of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, People’s Republic of China; 5Department of Physics, University of Saarland, Saarbruechen, Germany; *These authors have contributed equally to this workAbstract: This study aims to evaluate the multidrug resistance (MDR) reversal activity by magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) and 5-bromotetrandrine (BrTet) MDR cell line K562/A02 solitarily or symphysially. The proliferation of K562 and K562/A02 cells and the cytotoxicity on peripheral blood mononuclear cells (PMBCs) were evaluated by MTT assay. Cellular accumulation of daunorubicin (DNR) was analyzed by flow cytometry. Real-time polymerase chain reaction and Western blotting analyses were performed to examine the mRNA and protein levels of mdr1, respectively. The results showed that the combination of MNPs-Fe3O4 and BrTet with effective concentrations significantly increased cytotoxicity against MDR cell line K562/A02. Both BrTet and MNPs-Fe3O4 increased the intracellular DNR accumulation in the K562/A02 cell line, and downregulated the level of mdr1 gene and expression of P-glycoprotein. Furthermore, the combination did not have significant cytotoxicity in PMBCs. We propose that MNPs-Fe3O4 conjugated with DNR and BrTet probably have synergetic effects on MDR reversal.Keywords: magnetic nanoparticles of Fe3O4, 5-bromotetrandrine, multidrug resistance K562/A02