05). As predicted, the SHP099 solubility dmso expression of CDK8 was also correlated with the expression of β-catenin in both tumor tissues (r = 0.485, P < 0.05) and adjacent normal tissues (r = 0.346, P < 0.05). Figure 7 CDK8 and β-catenin protein expression in colon tumor and adjacent normal tissues detected by IHC. The expression of CDK8 (left) and β-catenin (right) was stained brown and present in tumor tissue and adjacent normal tissues. Representative Smoothened inhibitor sites with negative (a, 400 X ), moderate positive (c, 400 × ),

strongly positive (e, 400 ×) expression of CDK8 and corresponding weakly positive (b, 400 ×), moderate positive (d, 400 ×), strongly positive (f, 400 ×) expression of β-catenin. Discussion Aberrant activation of the Wnt/β-catenin pathway has been shown to be associated with numerous human cancers [1, 2, 16]. Previous studies revealed that an abnormality in β-catenin signaling pathway may be responsible for almost all types of colon cancers [4, 17]. It has been reported that CDK8 plays a central role in the www.selleckchem.com/products/iwp-2.html regulation of β-catenin activation [3, 18]. Based on such a background, further exploring of the role of CDK8 and β-catenin in the oncogenesis and progression of colon cancer as well as their correlation, not only provides

a broad understanding of the etiology of colon cancer, but also may provide an intervention stategy with Phospholipase D1 CDK8 and β-catenin as a target. Ron Firestein et al [8] found that CDK8 was necessary for the β-catenin-mediated activation of proto-oncogenes. They noted that, in the absence of CDK8, the activity of β-catenin-mediated transcription was significantly decreased, whereas an overexpression of CDK8 could induce proto-oncogene activation [19]. Additionally, Morris and colleagues screened E2F1-dependent apoptotic genes and found that E2F1 could inhibit Wnt/β-catenin activity and CDK8 was the most potential inhibitor of E2F1

[9, 19]. Furthermore, CDK8 may also be involved in other signaling pathways. It is reported that CDK8 is a positive co-stimulatory regulator of the expression of p53 gene [20] and p53′s downstream gene p21 since the binding of CDK8 to the p53 gene can increase its transcription activity. Furthermore, CDK8 could regulate the Notch signaling pathway [21] and exerted positive regulatory effects on the tumorigenicity related mRNA prolongation [22]. Therefore, CDK8 may be considered to be a proto-oncogene based on the above observations. To investigate the effects of the activity of β-catenin on colon cancer through CDK8, CDK8 interference was constructed and transfected in colon cancer cells CT116 by the application of siRNA in our study. The alteration of the expression of β-catenin, proliferation, cell apoptosis and cell cycle distribution in HCT116 cells were determined.