title: Antitumor efficacy of DMSA modified Fe3O4 magnetic nanoparticles combined with arsenic trioxide and adriamycin in Raji cells.
abstract: The objective of the present study was to investigate the anticancer efficacy of dimercaptosuccinic acid modified iron oxide (DMSA-Fe3O4) magnetic nanoparticles (MNPs) combined with arsenic trioxide (As2O3) and doxorubicin (ADM) in non-Hodgkin's lymphoma (NHL) cell line (Raji cells). The growth inhibition rate of Raji cells was determined by MTT assay. Characteristics of DMSA-Fe3O4 MNPs and distribution of nanoparticles taken up by Raji cells were observed under a transmission electron microscopy (TEM). Further, apoptosis of cells and intracellular concentration of ADM were detected by flow cytometry (FCM). DAPI staining was used to view apoptotic cellular morphology. Subsequently, transcription and protein expression levels of bcl-2, NFKB, survivin, bax, p53 and caspase-3 were determined by reverse transciptase polymerase chain reaction (RT-PCR) and Western blotting analysis, respectively. The results of MTT assay indicated that the inhibition of Raji cells by the combined form of ADM and As2O3 was significantly higher than either ADM or As2O3 alone. However, ADM-As2O3 MNPs proved superior over all other groups. TEM observation revealed that the majority of MNPs were quasi-spherical with an average diameter of about 18 nm and the MNPs taken up by cells were located in the endosome vesicles of cytoplasm. The apoptotic rate and accumulation of intracellular ADM in ADM-As2O3 MNPs group were significantly higher than those in control, ADM, As2O3 and ADM+As2O3, groups. In addition, DAPI staining of Raji cells from ADM-As,O3 MNPs group clearly exhibited more morphological changes (severe structural alterations) than other groups. Moreover, transcription and protein expression of bcl-2, NFKB, survivin, bax, p53 and caspase-3 of Raji cells were regulated at the most remarkable extent in ADM-As2O3, MNPs group as compared with other groups. These findings suggest that the antitumor efficacy of the combination of novel ADM-As2O3, MNPs on Raji cells would be a promising strategy for lymphoma therapy.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Cai
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Cai
authors.forename: Chunling
authors.initials: C
authors.lastname: Wang
authors.forename: Baoan
authors.initials: B
authors.lastname: Chen
authors.forename: Weijun
authors.initials: W
authors.lastname: Hua
authors.forename: Fei
authors.initials: F
authors.lastname: Shen
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.forename: Zhengmei
authors.initials: Z
authors.lastname: He
authors.forename: Yuye
authors.initials: Y
authors.lastname: Shi
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Guohua
authors.initials: G
authors.lastname: Xia
authors.forename: Wen
authors.initials: W
authors.lastname: Bao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D005290:Ferric Compounds / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010087:Oxides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D004113:Succimer / Q000737:chemistry*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; C107489:BIRC5 protein, human; D005290:Ferric Compounds; D051034:Inhibitor of Apoptosis Proteins; D058185:Magnetite Nanoparticles; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C000499:ferric oxide; D004317:Doxorubicin; D004113:Succimer; D053148:Caspase 3; D000077237:Arsenic Trioxide