Chuffa, Luiz Gustavo de Almeida [UNESP]Fioruci-Fontanelli, Beatriz Aparecida [UNESP]Mendes, Leonardo de Oliveira [UNESP]Seiva, Fábio Rodrigues FerreiraMartinez, MarceloFavaro, Wagner JoséDomeniconi, Raquel Fantin [UNESP]Pinheiro, Patricia Fernanda Felipe [UNESP]Santos, Lucilene Delazari dos [UNESP]Martinez, Francisco Eduardo2015-10-212015-10-212015-02-06Bmc Cancer. London: Biomed Central Ltd, v. 15, p. 1-13, 2015.1471-2407http://hdl.handle.net/11449/128549Background: Toll-like receptors (TLRs) are effector molecules expressed on the surface of ovarian cancer (OC) cells, but the functions of the TLR2/TLR4 signaling pathways in these cells remain unclear. Melatonin (mel) acts as an anti-inflammatory factor and has been reported to modulate TLRs in some aggressive tumor cell types. Therefore, we investigated OC and the effect of long-term mel therapy on the signaling pathways mediated by TLR2 and TLR4 via myeloid differentiation factor 88 (MyD88) and toll-like receptor-associated activator of interferon (TRIF) in an ethanol-preferring rat model.Methods: To induce OC, the left ovary of animals either consuming 10% (v/v) ethanol or not was injected directly under the bursa with a single dose of 100 mu g of 7,12-dimethylbenz(a) anthracene (DMBA) dissolved in 10 mu L of sesame oil. The right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of mel (200 mu g/100 g b.w./day) for 60 days.Results: Although mel therapy was unable to reduce TLR2 levels, it was able to suppress the OC-associated increase in the levels of the following proteins: TLR4, MyD88, nuclear factor kappa B (NFkB p65), inhibitor of NFkB alpha (IkB alpha), IkB kinase alpha (IKK-alpha), TNF receptor-associated factor 6 (TRAF6), TRIF, interferon regulatory factor 3 (IRF3), interferon beta (IFN-beta), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL)-6. In addition, mel significantly attenuated the expression of IkB alpha, NFkB p65, TRIF and IRF-3, which are involved in TLR4-mediated signaling in OC during ethanol intake.Conclusion: Collectively, our results suggest that mel attenuates the TLR4-induced MyD88- and TRIF-dependent signaling pathways in ethanol-preferring rats with OC.1-13engOvarian cancerMelatoninInflammationTLR4MyD88TRIFArtigo10.1186/s12885-015-1032-4WOS:000349182200001Acesso abertoWOS000349182200001.pdf512131967650303454817565282994691739564105219382576056097075159833684041266959110000-0003-1452-57080000-0003-2938-010X