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Differential drug resistance acquisition to doxorubicin and paclitaxel in breast cancer cells
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  • 作者:Feifei Xu ; Fengliang Wang ; Ting Yang ; Yuan Sheng ; Ting Zhong…
  • 关键词:Multi ; drug Resistance Acquisition (MDR) ; P ; glycoprotein (P ; gp) ; Drug ; specific ; Doxorubicin (DOX) ; Paclitaxel (PTX)
  • 刊名:Cancer Cell International
  • 出版年:2014
  • 出版时间:December 2014
  • 年:2014
  • 卷:14
  • 期:1
  • 全文大小:2,797 KB
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  • 刊物主题:Cancer Research; Cell Biology;
  • 出版者:BioMed Central
  • ISSN:1475-2867
文摘
Background Several signal transduction pathways have been reported being involved in the acquisition of P-glycoprotein (P-gp) mediated multi-drug resistance (MDR) upon exposure to anti-cancer drugs, whereas there is evidence indicating that the expression and activity of P-gp were not equally or even reversely modulated by different drugs. Methods To further illustrate this drug-specific effect, possible mechanisms that enable breast cancer cells MCF-7 to acquire MDR to either paclitaxel (PTX) or doxorubicin (DOX) were investigated in a time-dependent manner. Results The results suggested that at least two pathways participated in this process. One was the short and transient activation of NF-κB, the second one was the relatively prolonged induction of PXR. Both PXR and NF-κB pathways took part in the PTX drug resistance acquisition, whereas DOX did not exert a significant effect on the PXR-mediated induction of P-gp. Furthermore, the property of NF-κB activation shared by DOX and PTX was not identical. An attempt made in the present study demonstrated that the acquired resistance to DOX was via or partially via NF-κB activation but not its upstream receptor TLR4, while PTX can induce the drug resistance via TLR4-NF-κB pathway. Conclusions To our knowledge, this report is among the first to directly compare the time dependence of NF-κB and PXR pathways. The current study provides useful insight into the distinct ability of DOX and PTX to induce P-gp mediated MDR in breast cancer. Different strategies may be required to circumvent MDR in the presence of different anti-cancer drugs.

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