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Downregulation of Wnt3 Suppresses Colorectal Cancer Development Through Inhibiting Cell Proliferation and Migration.

ABSTRACT: The aberrant expression of Wnt3 has linked to several types of human malignancies. However, it is not known for its role in tumorigenesis of colorectal cancer (CRC). Herein, we show that Wnt3 is upregulated in human CRC tissues and is essential for the CRC progression. Knockdown of Wnt3 in human CRC cells delayed tumor formation in nude mouse xenografts through silencing of canonical Wnt pathway and glycolysis. We further found that silencing of Wnt3 enhanced the sensitivity of CRC cells to cisplatin through inducing apoptotic cell death. Taken together, it demonstrates that Wnt3 is a novel clinical biomarker for the detection of CRC and plays an important role in colorectal tumorigenesis. Therefore, downregulation of Wnt3 will be a valuable strategy in CRC treatment.

SUBMITTER: Nie X

PROVIDER: S-EPMC6779829 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Downregulation of Wnt3 Suppresses Colorectal Cancer Development Through Inhibiting Cell Proliferation and Migration.

Nie Xiaobo X Xia Fulin F Liu Ying Y Zhou Yun Y Ye Wenling W Hean Panha P Meng Jiming J Liu Huiyang H Liu Lei L Wen Jianxun J Ren Xuequn X Chen Wei-Dong WD Wang Yan-Dong YD

Frontiers in pharmacology 20191001

The aberrant expression of Wnt3 has linked to several types of human malignancies. However, it is not known for its role in tumorigenesis of colorectal cancer (CRC). Herein, we show that Wnt3 is upregulated in human CRC tissues and is essential for the CRC progression. Knockdown of Wnt3 in human CRC cells delayed tumor formation in nude mouse xenografts through silencing of canonical Wnt pathway and glycolysis. We further found that silencing of Wnt3 enhanced the sensitivity of CRC cells to cisp ...[more]

PMID: 31632267

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Project description:Colorectal cancer (CRC) is one of the leading causes of cancer?associated mortality. Asiaticoside (AC) exhibits antitumor effects; however, to the best of our knowledge, the biological function of AC in CRC cells remains unclear. Therefore, the aim of the present study was to investigate the effect of AC on CRC cells. In the present study, CCK?8 and colony formation assays were performed to assess the effects of AV on human CRC cell lines (HCT116, SW480 and LoVo). Mitochondrial membrane potential was examined by JC?1 staining. Cell apoptosis and cell cycle were monitored by flow cytometry, and the expression of genes was evaluated using RT?qPCR and western blot analysis. Furthermore, the biological effect of AC in vivo was detected using a xenograft mouse model. The findings revealed that 2 µM AC suppressed the proliferation of CRC cells in a time? and dose?dependent manner, but had no adverse effects on normal human intestinal FHC cells at a range of concentrations. AC decreased the mitochondrial membrane potential and increased the apoptosis of CRC cells in a dose?dependent manner. Furthermore, AC induced cell cycle arrest at the G0/G1 phase. AC attenuated I?B? phosphorylation in a dose?dependent manner, thereby preventing P65 from entering the nucleus, and resulting in inhibition of the NF??B signaling pathway. In addition, AC significantly reduced the expression of CDK4 and Cyclin D1 in a dose?dependent manner, significantly upregulated the activation of caspase?9 and caspase?3, and decreased the Bcl?2/Bax mRNA ratio. Furthermore, treatment with the NF??B signaling pathway inhibitor JSH?23 significantly increased the cytotoxicity of AC in CRC cells. Findings of the xenograft mice model experiments revealed that AC significantly inhibited colorectal tumor growth in a dose?dependent manner. Overall, AC suppressed activation of the NF??B signaling pathway by downregulating I?B? phosphorylation. This resulted in inhibition of CRC cell viability and an increase of cell apoptosis, which may form the basis of AC use in the treatment of patients with CRC.

Dataset Information

Downregulation of Wnt3 Suppresses Colorectal Cancer Development Through Inhibiting Cell Proliferation and Migration.

Publications

Downregulation of Wnt3 Suppresses Colorectal Cancer Development Through Inhibiting Cell Proliferation and Migration.

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