期刊
JOURNAL OF CANCER
卷 5, 期 9, 页码 728-735出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.10196
关键词
Ovarian cancer; melatonin; Her-2; p38 MAPK; p-AKT; mTOR
类别
资金
- FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [Proc. 2013/10309-9, 2013/02466-7]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [13/02466-7] Funding Source: FAPESP
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据