Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats

Autor(es)

Ferreira, Grazielle M. ^[1] ; Martinez, Marcelo ^[2] ; Camargo, Isabel Cristina C. ^[3] ; Domeniconi, Raquel F. ^[1] ; Martinez, Francisco Eduardo ^[1] ; Chuffa, Luiz Gustavo A. ^[1]

Afiliação do(s) autor(es)

^[1] UNESP Univ Estadual Paulista, Dept Anat, Biosci Inst, BR-18618970 Botucatu, SP - Brazil

^[2] UFSCar Univ Fed Sao Carlos, Dept Morphol & Pathol, BR-13565905 Sao Carlos, SP - Brazil

^[3] UNESP Univ Estadual Paulista, Dept Biol Sci, Fac Sci & Letters, BR-19806900 Assis, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CANCER; v. 5, n. 9, p. 728-735, 2014.
• Citações Web of Science: 27

Resumo

Epidermal growth factor receptors 2 (Her-2) and 4 (Her-4) are closely associated with ovarian cancer (OC) progression and metastasis, and a more complete understanding of these signaling pathways allow the development of new therapeutic strategies. Melatonin (Mel) is recognized as having several anticancer properties and has been reported to modulate Her-2 system in aggressive tumors. Here, we investigated OC and the role of Mel therapy on the Her-2- and Her-4-signaling pathway related to downstream molecules in an ethanol-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 mu g 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 mu L of sesame oil under the bursa. 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. While Mel therapy was unable to reduce Her-4 and phosphoinositide 3-kinase (PI3K) levels, it was able to suppress the OC-related increase in the levels of the Her-2, p38 mitogen-activated protein kinases (p38 MAPK), protein kinase B (phospho-AKT), and mammalian target of rapamycin (mTOR). In addition, Mel significantly attenuated the expression of Her-2, p38 MAPK, and p-AKT, which are involved in OC signaling during ethanol intake. Collectively, our results suggest that Mel attenuates the Her-2-signaling pathway in OC of ethanol-preferring rats, providing an effective contribution for further development of adjuvant therapies. (AU)

• Processo FAPESP: 13/02466-7 - Indução tumoral ovariana e influência da melatonina sobre o processo inflamatório via sinalização mediada pelo receptor Toll-like 4 em ratas UChB
• Beneficiário: Luiz Gustavo de Almeida Chuffa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/10309-9 - Indução tumoral ovariana e influência da melatonina sobre a via de sinalização mediada pelos receptores Her 2 e 4 em ratas UChB
• Beneficiário: Grazielle de Moura Ferreira
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica