Inhibition of cell proliferation and tumor growth of colorectal cancer by inhibitors of Wnt and Notch signaling pathways.

ABSTRACT

Understanding the role and mechanism of signaling pathways including Notch and Wnt in colorectal carcinogenesis is critical to the development of novel therapeutics. In the present study, we analyzed the cell proliferation, migration, G2/M percentage and the expression of molecules of signaling pathways in HCT-116 cells through the inhibition of Wnt and Notch pathways, and also investigated the effect of inhibitors of Wnt and Notch pathways on tumor growth in a transplantation tumor model. We observed that rDDK-1 (an inhibitor of the Wnt signaling pathway) and LY374973 (an inhibitor of the Notch signaling pathway) synergistically inhibited the proliferation, migration and G2/M percentage of HCT-116 cell lines, and could further synergistically inhibit the tumor volume and weight in the transplantation tumor model. In the cell line and the transplantation tumor model, rDDK-1 and LY374973 further synergistically inhibited the expression level of all detected Wnt and Notch pathway genes. Our results may pave the way for using inhibitors of Wnt and Notch signaling pathways together to treat colorectal cancer.