A leukotriene B 4 receptor-2 is associated with paclitaxel resistance in MCF-7/DOX breast cancer cells

H. Kim, G. S. Park, J. E. Lee, Jae-Hong Kim

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background:Breast cancer is the most common malignancy in women. Although chemotherapeutic agents, such as paclitaxel, are effective treatments for the majority of breast cancer patients, recurrence is frequent and often leads to death. Thus, there is an urgent need to identify novel therapeutic targets that sensitise tumour cells to existing chemotherapy agents.Methods:The levels of leukotriene B 4 receptor-2 (BLT2) in multidrug-resistant MCF-7/DOX cells were determined using quantitative PCR and FACS analysis. The potential role of BLT2 in the paclitaxel resistance of MCF-7/DOX cells was assessed using a pharmacological inhibitor and small interfering RNA knockdown, and the BLT2-associated resistance mechanism was assessed.Results:The expression levels of BLT2 were markedly upregulated in MCF-7/DOX cells. The inhibition of BLT2 by pre-treatment with LY255283 or siBLT2 knockdown significantly sensitised MCF-7/DOX cells to paclitaxel and induced significant levels of apoptotic death, suggesting that BLT2 mediates paclitaxel resistance. We also demonstrated that BLT2-induced paclitaxel resistance was associated with the upregulation of P-glycoprotein. Finally, co-treatment with a BLT2 inhibitor and paclitaxel markedly reduced tumour growth in an MCF-7/DOX in vivo model.Conclusion: Together, our results demonstrate that BLT2 is a novel therapeutic target that sensitises drug-resistant breast cancer cells to paclitaxel.

Original languageEnglish
Pages (from-to)351-359
Number of pages9
JournalBritish Journal of Cancer
Volume109
Issue number2
DOIs
Publication statusPublished - 2013 Jul 23

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Keywords

  • BLT2
  • breast cancer
  • multidrug resistance
  • P-glycoprotein
  • paclitaxel resistance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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