Title |
Axitinib Targeted Cancer Stemlike Cells to Enhance Efficacy of Chemotherapeutic Drugs via Inhibiting the Drug Transport Function of ABCG2
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Published in |
Molecular Medicine, April 2012
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DOI | 10.2119/molmed.2011.00444 |
Pubmed ID | |
Authors |
Fang Wang, Yan-jun Mi, Xing-Gui Chen, Xing-ping Wu, Zhenguo Liu, Shu-peng Chen, Yong-ju Liang, Chao Cheng, Kenneth Kin Wah To, Li-wu Fu |
Abstract |
Stemlike cells have been isolated by their ability to efflux Hoechst 33342 dye and are called the side population (SP). We evaluated the effect of axitinib on targeting cancer stemlike cells and enhancing the efficacy of chemotherapeutical agents. We found that axitinib enhanced the cytotoxicity of topotecan and mitoxantrone in SP cells sorted from human lung cancer A549 cells and increased cell apoptosis induced by chemotherapeutical agents. Moreover, axitinib particularly inhibited the function of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) and reversed ABCG2-mediated multidrug resistance (MDR) in vitro. However, no significant reversal effect was observed in ABCB1-, ABCC1- or lung resistance-related protein (LRP)-mediated MDR. Furthermore, in both sensitive and MDR cancer cells axitinib neither altered the expression of ABCG2 at the mRNA or protein levels nor blocked the phosphorylation of AKT and extracellular signal-regulated kinase (ERK)1/2. In nude mice bearing ABCG2-overexpressing S1-M1-80 xenografts, axitinib significantly enhanced the antitumor activity of topotecan without causing additional toxicity. Taken together, these data suggest that axitinib particularly targets cancer stemlike cells and reverses ABCG2-mediated drug resistance by inhibiting the transporter activity of ABCG2. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 4% |
Portugal | 1 | 4% |
Unknown | 23 | 92% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 7 | 28% |
Professor > Associate Professor | 4 | 16% |
Student > Ph. D. Student | 3 | 12% |
Student > Doctoral Student | 2 | 8% |
Student > Master | 2 | 8% |
Other | 4 | 16% |
Unknown | 3 | 12% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 5 | 20% |
Agricultural and Biological Sciences | 5 | 20% |
Medicine and Dentistry | 5 | 20% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 16% |
Chemistry | 2 | 8% |
Other | 2 | 8% |
Unknown | 2 | 8% |