Relationship between epithelial cell adhesion molecule and wingless/integrated-β-catenin signaling in colon cancer and the effect of XAV939 on the expression of related markers

Abstract

Objective To investigate whether activation of Wingless/integrated-β-catenin (Wnt-β-catenin) pathway regulates epithelial cell adhesion molecule (EpCAM) expression in colon cancer and analyze the effect of XAV939 on colon cancer-associated markers. Methods After Wnt-β-catenin signaling was activated, relative expression levels of related genes were determined by quantitative real-time polymerase chain reaction (RT-qPCR). After constructing a mouse colon cancer model, XAV939 and/or 5-Fu were intraperitoneally injected for 1 week. Detection of related molecules expression in colon tissue by Western blotting. Results Compared with the control group, LiCl could significantly stimulate the expression of Wnt-β-catenin signaling pathway genes, and the levels of TACSTD1, DKK1, BAMBI, CCND1 and MYC genes were significantly increased by 1.20-, 2.44-, 4.34-, 2.57-, 1.58 fold (t=12.179, 20.661, 54.378, 19.384, 20.341, P<0.05), respectively. ZnCl2 treatment significantly inhibited the expression of TACSTD1 and CCND1 in HCT116 cells (tTACSTD1=36.467, 9.682, tCCND1=16.130, 17.003, P<0.05), which were down-regulated by about 50.06% and 34.38%, respectively. In the APC gene-deficient cells, the inhibitory effect of ZnCl2 on TACSTD1 and CCND1 was reversed. XAV939 and XAV939+ 5-fluorouracil (5-Fu) treatment significantly up-regulated the expression of Axin in HCT116 cells, which was about 15.97 and 17.2 fold higher than that of the control group (t=19.502, 18.236, P<0.05); and expression of β-catenin, EpCAM, telomerase reverse transcriptase (TERT) and bicorticosteroids and calmodulin dependent protein kinase-like 1 (DCAMKL-1) were down-regulated by 0.75 and 0.72 fold, 0.68 and 0.25 fold, 0.74 and 0.73 fold, 0.27 and 0.34 fold (tβ-catenin=20.412, 22.862, tEpCAM=26.336, 27.111, 82.711, tTERT=19.636, 22.787, 23.678, tDCAMKL-1=81.637, 64.814, P<0.05), respectively. Conclusion XAV939 inhibits tumor cell proliferation by blocking Wnt-β-catenin signaling down-regulation of β-catenin, target gene EpCAM and other related factors of CSC to promote colon cancer prognosis. Key words: Wingless/Integrated-β-catenin pathway; Epithelial cell adhesion molecule; XAV939; Colon cancer