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

Fingerprint

Leukotriene B4
Paclitaxel
Breast Neoplasms
MCF-7 Cells
LY 255283
Therapeutics
Neoplasms
P-Glycoprotein
Small Interfering RNA
Up-Regulation
Pharmacology
Recurrence
Drug Therapy
Polymerase Chain Reaction
Growth
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A leukotriene B 4 receptor-2 is associated with paclitaxel resistance in MCF-7/DOX breast cancer cells. / Kim, H.; Park, G. S.; Lee, J. E.; Kim, Jae-Hong.

In: British Journal of Cancer, Vol. 109, No. 2, 23.07.2013, p. 351-359.

Research output: Contribution to journalArticle

@article{2f902d1bb48845a28a899a39efb8ab55,
title = "A leukotriene B 4 receptor-2 is associated with paclitaxel resistance in MCF-7/DOX breast cancer cells",
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.",
keywords = "BLT2, breast cancer, multidrug resistance, P-glycoprotein, paclitaxel resistance",
author = "H. Kim and Park, {G. S.} and Lee, {J. E.} and Jae-Hong Kim",
year = "2013",
month = "7",
day = "23",
doi = "10.1038/bjc.2013.333",
language = "English",
volume = "109",
pages = "351--359",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - A leukotriene B 4 receptor-2 is associated with paclitaxel resistance in MCF-7/DOX breast cancer cells

AU - Kim, H.

AU - Park, G. S.

AU - Lee, J. E.

AU - Kim, Jae-Hong

PY - 2013/7/23

Y1 - 2013/7/23

N2 - 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.

AB - 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.

KW - BLT2

KW - breast cancer

KW - multidrug resistance

KW - P-glycoprotein

KW - paclitaxel resistance

UR - http://www.scopus.com/inward/record.url?scp=84881088557&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881088557&partnerID=8YFLogxK

U2 - 10.1038/bjc.2013.333

DO - 10.1038/bjc.2013.333

M3 - Article

C2 - 23799854

AN - SCOPUS:84881088557

VL - 109

SP - 351

EP - 359

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 2

ER -