Bioquímica e Farmacologia: Acesso Aberto
Acesso livre
ISSN: 2167-0501
ISSN: 2167-0501
Noura M Darwish*, Fahad A Al-Dhabaan, Ahmed Sultan, Ahmed Malki, and Mohamed Soliman Elshikh
Background: Aberrant activation of the Ras/Raf-1/extracellular-regulated kinase (ERK) pathway has been shown to be involved in the progression of hepatocellular carcinoma (HCC). However, the mechanism of dysregulation of ERK activation is poorly understood. This study aimed to investigate the inhibitory effect of novel 3D-organocopper supramolecular coordination polymer (SCP) on invasive potential of hepatocellular carcinoma (HCC) cells and to explore the underlying mechanism. Chemoprevention could represent an important means to inhibit the process of hepatocarcinogenesis.
Methods: The inhibitory effect of SCP compound on hepatoma cells was evaluated by the examination of HCC chemically induced liver tissues and specific pathway inhibition was examined by immunohistochemistry.
Results: Recently, we identified the newly synthesized SCP as a potent inhibitor of the Ras/Raf-1/ERK pathway. In this study, we found that the expression levels of ERK1 and-2 in chemically induced HCC tissue was frequently decreased in response to SCP treatment, comparing with those untreated with SCP compound. Moreover, ERK expression levels in HCC tissue were frequently correlated with the incidence of tumor invasion and metastasis. Increased expression of beta catenin in liver tissue, which was associated with increased ERK activation. P-ERK1/2 overexpression also reduced the expression of E-cadherin, which play important roles in tumor invasion and metastasis.
Conclusion: We concluded that SCP can effectively inhibit the invasive potential of ERK signaling pathway and ERK could be not only a novel prognostic factor but also a new therapeutic target for human HCC.