Leukotriene B4 receptor-2 contributes to chemoresistance of SK-OV-3 ovarian cancer cells through activation of signal transducer and activator of transcription-3-linked cascade

Jae In Park; Soo Young Park; Jae Hong Kim

doi:10.1016/j.bbamcr.2015.11.011

Leukotriene B₄ receptor-2 contributes to chemoresistance of SK-OV-3 ovarian cancer cells through activation of signal transducer and activator of transcription-3-linked cascade

Jae In Park, Soo Young Park, Jae Hong Kim

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

Inflammation and inflammatory mediators are intimately linked with chemoresistance through complex pathways in the tumor microenvironment. However, the mechanism by which inflammatory mediators (e.g., eicosanoids) contribute to chemoresistance remains elusive. In this study, we found that the low-affinity leukotriene B₄ receptor-2 (BLT2) and its ligand leukotriene B₄ were highly up-regulated in cisplatin-resistant SK-OV-3 ovarian cancer cells and play critical roles in mediating the chemoresistance through the activation of signal transducer and activator of transcription-3 (STAT-3) and the subsequent up-regulation of interleukin-6 (IL-6). BLT2 depletion with siRNA clearly abolished the chemoresistance to cisplatin in SK-OV-3 ovarian cancer cells and further increased cell sensitivity to cisplatin chemotherapy by down-regulating the 'STAT-3-IL-6' cascade. Enlarged tumor formation due to the cisplatin resistance of SK-OV-3 cells in cisplatin-treated athymic mice was also substantially reduced by co-treatment with the BLT2 inhibitor in vivo. Our study demonstrates that BLT2 is a novel contributor to cisplatin resistance in SK-OV-3 ovarian cancer cells and thus may be a potential therapeutic target for the treatment of cisplatin-resistant ovarian cancer.

Original language	English
Pages (from-to)	236-243
Number of pages	8
Journal	Biochimica et Biophysica Acta - Molecular Cell Research
Volume	1863
Issue number	2
DOIs	https://doi.org/10.1016/j.bbamcr.2015.11.011
Publication status	Published - 2016 Feb 1

Bibliographical note

Funding Information:
This work was supported by Bio & Medical Technology Development Program Grant ( 2012M3A9C5048709 , 2012M3A9C1053532 ) through the National Research Foundation (NRF) funded by the Ministry of Science , Information and Communication Technologies (ICT) and Future Planning, Republic of Korea. Also, this work was supported by Basic Science Research Program ( 2015R1D1A1A01057757 ) through NRF funded by the Ministry of Education. This work was also supported by a Korea University Grant and BK21 Plus Program (School of Life Sciences and Biotechnology, Korea University).

Publisher Copyright:
© 2015 Elsevier B.V.

Keywords

BLT2
Chemoresistance
Cisplatin
Ovarian cancer
SK-OV-3 cells
STAT-3

ASJC Scopus subject areas

Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bbamcr.2015.11.011

Cite this

Leukotriene B₄ receptor-2 contributes to chemoresistance of SK-OV-3 ovarian cancer cells through activation of signal transducer and activator of transcription-3-linked cascade. / Park, Jae In; Park, Soo Young; Kim, Jae Hong.
In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1863, No. 2, 01.02.2016, p. 236-243.

Research output: Contribution to journal › Article › peer-review

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abstract = "Inflammation and inflammatory mediators are intimately linked with chemoresistance through complex pathways in the tumor microenvironment. However, the mechanism by which inflammatory mediators (e.g., eicosanoids) contribute to chemoresistance remains elusive. In this study, we found that the low-affinity leukotriene B4 receptor-2 (BLT2) and its ligand leukotriene B4 were highly up-regulated in cisplatin-resistant SK-OV-3 ovarian cancer cells and play critical roles in mediating the chemoresistance through the activation of signal transducer and activator of transcription-3 (STAT-3) and the subsequent up-regulation of interleukin-6 (IL-6). BLT2 depletion with siRNA clearly abolished the chemoresistance to cisplatin in SK-OV-3 ovarian cancer cells and further increased cell sensitivity to cisplatin chemotherapy by down-regulating the 'STAT-3-IL-6' cascade. Enlarged tumor formation due to the cisplatin resistance of SK-OV-3 cells in cisplatin-treated athymic mice was also substantially reduced by co-treatment with the BLT2 inhibitor in vivo. Our study demonstrates that BLT2 is a novel contributor to cisplatin resistance in SK-OV-3 ovarian cancer cells and thus may be a potential therapeutic target for the treatment of cisplatin-resistant ovarian cancer.",

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