title: 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.
authors.affiliation: Department of Graduate School, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China; Department of Gastroenterology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China; Department of Gastroenterology, The Second People's Hospital of Yunnan, Kunming, Yunan 650021, P.R. China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Foreign Language Department, Kunming Medical University, Kunming, Yunan 650032, P.R. China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunan 650032, P.R. China.
authors.forename: Yinglei
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Gastroenterology, The Second People's Hospital of Yunnan, Kunming, Yunan 650021, P.R. China.
authors.forename: Xikun
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Gastroenterology, The Second People's Hospital of Yunnan, Kunming, Yunan 650021, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Sha
keywords: Notch signaling pathway; Wnt signaling pathway; colorectal cancer