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Research Journal of Pharmacy and Technology
Year : 2019, Volume : 12, Issue : 12
First page : ( 5871) Last page : ( 5877)
Print ISSN : 0974-3618. Online ISSN : 0974-360X.
Article DOI : 10.5958/0974-360X.2019.01018.7

Selective Cyclooxygenase-2 Inhibitor Etoricoxib Attenuated Hypoxic Cancer Milieu induced M2-Polarization of Macrophages and Acquisition of Pro-angiogenic and Pro-invasive Attributes

Jain Nem Kumar1,23,*, Baghel Khemraj Singh1

1Division of Toxicology, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh-226031, India

2National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, Uttar Pradesh-229010, India

3School of Pharmacy, ITM University Gwalior, Gwalior, Madhya Pradesh, 475001

*Corresponding Author E-mail: nemjain.pharma@itmuniversity.ac.in

Online published on 18 July, 2020.

Abstract

Cyclooxygenase-2 (COX-2) inhibitors have been found to reduce the relative risk of breast cancer in several experimental and clinical studies. Various mechanisms of anti-tumor activity of COX-2 inhibition have been reported viz. anti-proliferation, apoptosis, preventing invasion and metastasis, and potentiation of anti-tumor immune responses. In addition to this, previous work indicated that attenuation of pro-tumoral M2 polarization of macrophages could be another mechanism of anti-cancer activity of COX-2 inhibitors. This prompted our investigation of the pro-tumoral M2 polarization inhibitory potential of Etoricoxib, a selective COX-2 blocker. Treatment with Etoricoxib markedly inhibited hypoxic breast cancer cell induced macrophage M2 polarization to a greater extent compared to Flunixin meglumine, a preferential COX-2 inhibitor. Moreover, we found that Etoricoxib treatment results in suppression of pro-angiogenic and pro-invasive functions of tumor associated macrophages (TAMs). Our study provides evidence for potential applicability of Etoricoxib as an anti-breast cancer modality via targeting M2 polarization of macrophages.

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Keywords

M2 Polarization, Hypoxia, COX-2, Etoricoxib, Flunixin meglumine, Pro-angiogenic, Pro-invasive, Tumor associated macrophages.

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