國家衛生研究院 NHRI:Item 3990099045/9910
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    题名: Desferal regulates hCtr1 and transferrin receptor expression through Sp1 and exhibits synergistic cytotoxicity with platinum drugs in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo
    作者: Chen, SJ;Kuo, CC;Pan, HY;Tsou, TC;Yeh, SC;Chang, JY
    贡献者: National Institute of Cancer Research;Institute of Biotechnology and Pharmaceutical Research;National Institute of Environmental Health Sciences
    摘要: The development of resistance to platinum drugs in cancer cells severely reduces the efficacy of these drugs. Thus, the discovery of novel drugs or combined strategies to overcome drug resistance is imperative. In addition to our previous finding that combined D-penicillamine with platinum drugs exerts synergistic cytotoxicity, we recently identified a novel therapeutic strategy by combining an iron chelating agent desferal with platinum drugs to overcome platinum resistance in an oxaliplatin-resistant human cervical cancer cell line, S3. Further study demonstrated that the level of platinum-DNA adduct formation positively correlated with cell death in combination of desferal with platinums than that of each drug alone in S3 cells. Decrement of human copper transporter 1 (hCtr1) and transferrin receptor 1 (TfR1) expression involved in the development of platinum resistance in S3 cells. Moreover, desferal promoted the expression of hCtr1 through the upregulation of Sp1. The overexpression of Sp1 increased the expression of NF-kappaB and translocated it into the nucleus to bind to the TfR1 promoter region, which subsequently increased the expression of TfR1. Importantly, the cotreatment of oxaliplatin with desferal significantly potentiated the oxaliplatin-elicited antitumoral effect in the oxaliplatin-resistant xenograft animal model without any toxic effect observed. Taken together, these results demonstrated that the combination of desferal with oxaliplatin can overcome oxaliplatin resistance through the regulation of hCtr1 and TfR1, and may have beneficial effect for treatment of patient with oxaliplatin-refractory tumors.
    日期: 2016-08
    關聯: Oncotarget. 2016 Aug;7(31):49310-49321.
    Link to: http://dx.doi.org/10.18632/oncotarget.10336
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000385422000039
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84981297960
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