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Shawn C. Maloney, Shriya Hari, Tamara Granner, Emilia Antecka, Cristina Miyamoto, Miguel N. Burnier, Jr.; Nicotinamide Treatment Decreases Secretion of Angiogenic and Inflammatory Cytokines in Uveal Melanoma Cell Lines. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6874. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Attenuation of angiogenic and inflammatory signalling in tumor cells is an important objective in many cancers, including uveal melanoma (UM). Nicotinamide (NIC) is a compound that has been shown to have anti-angiogenic properties in some cancer cell types. This study aimed to investigate the effects of NIC on the secretion of pro-angiogenic and pro-inflammatory cytokines in UM cell lines.
Two human UM cell lines (92.1 and OCM-1) were treated with NIC (10mM) or control media for 48 hours in culture. The supernatant from control and NIC conditions was used in sandwich ELISA-based angiogenesis and inflammation arrays to evaluate the effects of NIC on secretion of 20 pro-angiogenic and pro-inflammatory proteins. Samples were assayed in quadruplicate and a Student’s t-test with a significance cutoff of p<0.05 was used to determine statistical significance.
Seven pro-angiogenic cytokines were detected in control conditions for both UM cell lines while three were undetectable. Treatment with NIC caused a significant decrease in secretion of the following cytokines: Angiogenin, ANG2, EGF and VEGF-A in 92.1 cells; bFGF and HB-EGF in OCM-1 cells; PIGF in both cell lines. On inflammation arrays, MCP-1 and IL-8 had the highest levels of expression in both untreated cell lines and were significantly decreased in both cell lines following NIC treatment. No significant change was seen for the remaining eight inflammatory cytokines on the arrays.
Treatment of UM cell lines with NIC caused a reduction in secretion of several pro-angiogenic cytokines and differences were observed between cell lines. Additionally, NIC treatment significantly reduced expression of MCP-1 and IL-8 without up-regulating the other inflammatory cytokines assayed. These findings suggest that NIC has anti-angiogenic and anti-inflammatory effects on UM cells. This data provides the basis for further studies of NIC as a possible therapeutic agent in UM.
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