title: Differential drug resistance acquisition to doxorubicin and paclitaxel in breast cancer cells.
abstract: 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.
authors.affiliation: School of Pharmacy, Nanjing Medical University, 818 Tian Yuan East Road, Nanjing, 211166 China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004 China.
authors.forename: Fengliang
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Nanjing Medical University, 818 Tian Yuan East Road, Nanjing, 211166 China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Nanjing Medical University, 818 Tian Yuan East Road, Nanjing, 211166 China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: School of Pharmacy, Nanjing Medical University, 818 Tian Yuan East Road, Nanjing, 211166 China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhong
authors.affiliation: School of Pharmacy, Nanjing Medical University, 818 Tian Yuan East Road, Nanjing, 211166 China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
keywords: Doxorubicin (DOX); Drug-specific; Multi-drug Resistance Acquisition (MDR); P-glycoprotein (P-gp); Paclitaxel (PTX)