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Paclitaxel-Fe3O4 nanoparticles inhibit growth of CD138  CD34tumor stem-like cells in multiple myeloma-bearing mice

Authors Yang C, Wang J, Chen D, Chen J, Xiong F, Zhang H, Zhang Y, Gu N, Dou J

Received 23 September 2012

Accepted for publication 6 November 2012

Published 12 April 2013 Volume 2013:8(1) Pages 1439—1449

DOI https://doi.org/10.2147/IJN.S38447

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Cuiping Yang,1,3,* Jing Wang,2,* Dengyu Chen,1,* Junsong Chen,1 Fei Xiong,4 Hongyi Zhang,1 Yunxia Zhang,2 Ning Gu,4 Jun Dou1

1Department of Pathogenic Biology and Immunology, Medical School, 2Department of Gynecology and Obstetrics, Zhongda Hospital, Southeast University, Nanjing, 3Department of Pathogenic Biology and Immunology, School of Basic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 4School of Biological Science and Medical Engineering, Southeast University, Nanjing, People’s Republic of China

*These authors contributed equally to this work

Background: There is growing evidence that CD138 CD34 cells may actually be tumor stem cells responsible for initiation and relapse of multiple myeloma. However, effective drugs targeted at CD138 CD34 tumor stem cells are yet to be developed. The purpose of this study was to investigate the inhibitory effect of paclitaxel-loaded Fe3O4 nanoparticles (PTX-NPs) on CD138 CD34 tumor stem cells in multiple myeloma-bearing mice.
Methods: CD138 CD34 cells were isolated from a human U266 multiple myeloma cell line using an immune magnetic bead sorting method and then subcutaneously injected into mice with nonobese diabetic/severe combined immunodeficiency to develop a multiple myeloma-bearing mouse model. The mice were treated with Fe3O4 nanoparticles 2 mg/kg, paclitaxel 4.8 mg/kg, and PTX-NPs 0.64 mg/kg for 2 weeks. Tumor growth, pathological changes, serum and urinary interleukin-6 levels, and molecular expression of caspase-3, caspase-8, and caspase-9 were evaluated.
Results: CD138 CD34 cells were found to have tumor stem cell characteristics. All the mice developed tumors in 40 days after injection of 1 × 106 CD138 CD34 tumor stem cells. Tumor growth in mice treated with PTX-NPs was significantly inhibited compared with the controls (P <  0.005), and the groups that received nanoparticles alone (P < 0.005) or paclitaxel alone (P < 0.05). In addition, the PTX-NPs markedly inhibited interleukin-6 secretion, increased caspase-8, caspase-9, and caspase-3 expression, and induced apoptosis of tumor cells in the treated mice.
Conclusion: PTX-NPs proved to be a potent anticancer treatment strategy that may contribute to targeted therapy for multiple myeloma tumor stem cells in future clinical trials.

Keywords: multiple myeloma, tumor stem cells, Fe3O4 nanoparticles, paclitaxel

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