Downregulation of CDK-8 inhibits colon cancer hepatic metastasis by regulating Wnt/β-catenin pathway

Biomed Pharmacother. 2015 Aug:74:153-7. doi: 10.1016/j.biopha.2015.08.015. Epub 2015 Aug 15.

Abstract

Liver metastasis is a major cause of mortality from colon cancer. To investigate the role of cyclin-dependent kinase 8 (CDK8) in the progression of colon cancer hepatic metastasis. In this present study, human colon cancer HCT116 or HCT116-LUC-GFP cells were transfected with Lentiviral vector-mediated knockdown of CDK-8. After transfection, metastasis and invasion potential of colon cancer cell was investigated by wound healing and transwell invasion assays, respectively. A mice model of colon cancer liver metastases was established and observed with bioluminescence imaging. The protein expression of CDK-8, β-catenin, E2F1, MMP-7 and E-cadherin in liver tissues were detected by Western Blot. Our results revealed that lentiviral vector-mediated knockdown of CDK-8 inhibited metastasis and invasion of colon cancer cells in vitro and in vivo, respectively. Protein expression of CDK-8, β-catenin, MMP-7 and E-cadherin were inhibited, but protein expression of E2F1 was enhanced. In sum, our data provided compelling evidence that CDK-8 played a significant role in colon cancer hepatic metastasis by regulating the Wnt/β-catenin signal pathway and might sever as a potential therapeutic target for colon cancer patients.

Keywords: Bioluminescence imaging; CDK-8; Colon cancer; Hepatic metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Cyclin-Dependent Kinase 8 / genetics*
  • Disease Progression
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HCT116 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / secondary
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness / genetics
  • Transfection
  • Wnt Signaling Pathway / genetics*
  • Wound Healing / genetics

Substances

  • Cyclin-Dependent Kinase 8