Reversal in multidrug resistance by magnetic nanoparticle of Fe3O4 loaded with adriamycin and tetrandrine in K562/A02 leukemic cells.
Drug resistance is a primary hindrance for efficiency of chemotherapy. To investigate whether Fe3O4-magnetic nanoparticles (Fe3O4-MNPs) loaded with adriamycin (ADM) and tetrandrine (Tet) would play a synergetic reverse role in multidrug resistant cell, we prepared the drug-loaded nanoparticles by mechanical absorption polymerization to act with K562 and one of its resistant cell line K562/A02. The survival of cells which were cultured with these conjugates for 48 h was observed by MTT assay. Using cells under the same condition described before, we took use of fluorescence microscope to measure fluorescence intensity of intracellular ADM at an excitation wavelength of488 nm. P-glycoprotein (P-gp) was analyzed with flow cytometer. The expression ofmdrl mRNA was measured by RT-PCR. The results showed that the growth inhibition efficacy of both the two cells increased with augmenting concentrations of Fe3O4-MNPs which were loaded with drugs. No linear correlation was found between fluorescence intensity of intracellular adriamycin and augmenting concentration of Fe3O4-MNPs. Tet could downregulate the level of mdr-1 gene and decrease the expression of P-gp. Furthermore, Tet polymerized with Fe3O4-MNPs reinforced this downregulation, causing a 100-fold more decrease in mdrl mRNA level, but did not reduce total P-gp content. Our results suggest that Fe3O4-MNPs loaded with ADM or Tet can enhance the effective accumulation of the drugs in K562/A02. We propose that Fe3O4-MNPs loaded with ADM and Tet probably have synergetic effect on reversal in multidrug resistance.
Chen
Baoan
B
Department of Hematology, Zhongda Hospital, Southeast University, Nanjing, China.
Sun
Qian
Q
Wang
Xuemei
X
Gao
Feng
F
Dai
Yongyuan
Y
Yin
Yan
Y
Ding
Jiahua
J
Gao
Chong
C
Cheng
Jian
J
Li
Jingyuan
J
Sun
Xinchen
X
Chen
Ningna
N
Xu
Wenlin
W
Shen
Huiling
H
Liu
Delong
D
D000970:Antineoplastic Agents / Q000008:administration & dosage; D044182:Benzylisoquinolines / Q000008:administration & dosage*; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D018432:Drug Resistance, Multiple; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D020014:K562 Cells; D008280:Magnetics / Q000627:therapeutic use; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size
D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D004337:Drug Carriers; D005290:Ferric Compounds; C000499:ferric oxide; C009438:tetrandrine; D004317:Doxorubicin