Regulation of PKB/Akt-pathway in the chemopreventive effect of lactoferrin against diethylnitrosamine-induced hepatocarcinogenesis in rats

DOI Web Site

抄録

<p>Association of cancer with protein kinase B (PKB or Akt) activation and up-regulation has been recognized. PKB has significant effects on cell survival, angiogenesis, and cancer metastasis. Thus, PKB and many proteins in its pathway are considered as targets for cancer chemopreventives. Lactoferrin (Lf) has been reported for its inhibition of tumor growth and metastasis, however, the mechanism is not completely understood. Its anti-hepatocarcinogenic activity has not taken the deserved recognition despite the additional advantages reported for Lf as an antiviral against hepatitis C virus, the main cause of hepatocellular carcinoma (HCC), and as a targeting ligand for delivering chemotheraputics to hepatoma cells. This study evaluated the anti-hepatocarcinogenic effect of Lf (100, 200, or 400 mg/kg/day, p.o) and the role of PKB in this effect in HCC rat induced by diethylnitrosamine (DENA). Serum markers of liver function and hepatic oxidative and tumor markers, PKB, and endothelial nitric oxide synthase (eNOS) were assessed. Histopathological investigation and immunohistochemical analysis of liver cell proliferation, apoptosis, and expression of PKB and vascular endothelial growth factor (VEGF) were performed. The results revealed the induction of HCC in DENA-treated rats with an up-regulation and activation of hebatocytic PKB that was accompanied by increment of hepatic cell proliferation and expression of VEGF and eNOS, as well as inhibition of apoptosis. The role of PKB pathway in DENA-induced HCC was confirmed in vitro by the observed decrease in the number of viable cells, colony-forming ability and cell migration in a primary cell culture prepared from the DENA-induced hepatic lesions that was treated with PKB inhibitor. In vivo, a dose-dependent antihepatocarcinogenic effect of Lf was observed, with an inhibition of PKB, and alteration of its pathway-effector-proteins levels and other HCC-induced effects. These findings suggest regulation of PKB-pathway as a potential mechanism underlying Lf anticarcinogenic activity.</p>

収録刊行物

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ