Bindarit Attenuates Pain and Cancer-Related Inflammation by Influencing Myeloid Cells in a Model of Bone Cancer
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C–C motif chemokine ligand 2 (CCL2) is a small cytokine that functions in inflammation and cancer development. Bindarit, a CCL2 inhibitor, is a small anti-inflammatory molecule proven safe by phase II trials in type 2 diabetic nephropathy patients. As cancer-related inflammation is a cause of pain, we investigated whether Bindarit suppresses cancer-related inflammation and pain. We established a bone-cancer mouse model by inoculating cancer cells. After applying Bindarit, we preformed pain sensitivity tests and checked cancer development by X-ray. Using flow cytometry and qRT-PCR assays, we assessed the effect of Bindarit on peripheral blood monocyte mobilization and M2 macrophage polarization. We also investigated the targets of Bindarit using western blotting and luciferase assay. Bindarit-treated mice performed better in pain sensitivity tests compare to control mice. X-ray imaging showed that Bindarit-treated mice had fewer cancer cell colonies and smaller overall tumor burden. Bindarit reduced the number of monocytes in peripheral blood and down-regulated the expression of M2 macrophage polarization makers. Bindarit also inhibited IKKβ phosphorylation. Bindarit efficiently relieves cancer-related pain and suppresses cancer development. Bindarit inhibits monocyte mobilization in peripheral blood as well as M2 macrophage polarization. IKKβ is identified as a target of Bindarit.
KeywordsBindarit CCL2 Cancer Inflammation Pain
This work was supported by the Youth Fund of the Second Hospital of Shandong University (Y2013010049) and the Fund of Science and Technology Development Projects of Shandong Provence (No. 2012GSF11849).
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Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.