alexa NF-κB Inhibitor IMD-0354 Targets Human Non-Small Cell Lung Cancer Stem Cells and Combined with Chemotherapy Reduces Multidrug Resistance
ISSN: 1948-5956

Journal of Cancer Science & Therapy
Open Access

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Research Article

NF-κB Inhibitor IMD-0354 Targets Human Non-Small Cell Lung Cancer Stem Cells and Combined with Chemotherapy Reduces Multidrug Resistance

Azucena Gomez-Cabrero1*, Wolfgang Wrasidlo2 and Ralph A. Reisfeld1
1Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, USA
2Moores Cancer Center, University of California, San Diego, California, USA
Corresponding Author : Azucena Gomez-Cabrero
Department of Immunology and Microbial Sciences
The Scripps Research Institute, La Jolla, California 92037, USA
Tel: (+1) 858.784.8109/(+1) 858.232.3207
Fax: (+1) 858.784.2708
E-mail: agomezcabrero@hotmail.com; agomezc@scripps.edu
Received August 06, 2013; Accepted September 16, 2013; Published September 19, 2013
Citation: Gomez-Cabrero A, Wrasidlo W, Reisfeld RA (2013) NF-κB Inhibitor IMD-0354 Targets Human Non-Small Cell Lung Cancer Stem Cells and Combined with Chemotherapy Reduces Multidrug Resistance. J Cancer Sci Ther 5:300-312. doi:10.4172/1948-5956.1000220
Copyright: © 2013 Gomez-Cabrero A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

Most lung cancer patients are diagnosed at an advanced stage, when prognosis is poor. Multidrug resistance and tumor recurrence have been major reasons for these patients to succumb to the disease. Recent evidence points to cancer stem cells as being responsible for multidrug resistance and tumor repopulation as a result of their increased drug efflux and other stem cell-like properties. Thus, recent efforts have focused on targeting these cancer stem cells. Here, we combined liposomal nanoparticles targeted with a legumain inhibitor as a safe vehicle for drug delivery to the tumor microenvironment with Doxorubicin, a common chemotherapeutic agent that targets bulk cancer cells, and IMD-0354, an inhibitor of NF-κB targeting cancer stem cells. IMD-0354 decreased side populations, ABC transporters, stem-like and apoptosis resistance genes, and colony formation of human non-small cell lung cancer cells. In addition, IMD-0354 also had a cytotoxic effect on non-cancer stem cells and increased their apoptosis. The targeted delivery method, used previously in syngeneic mouse models enhanced drug delivery under hypoxia, a hallmark of the tumor microenvironment, but not under normoxia. Further, such targeted delivery reduced in vivo tumor burden in an aggressive model of human non-small cell lung cancer xenografts. Targeting of both bulk tumor cells and cancer stem cells with IMD-0354 as an adjuvant for chemotherapy are likely to reduce multidrug resistance and tumor recurrence, and thereby significantly reduce patient death from non-small cell lung cancer.

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