Curcumin inhibits tumor epithelial‑mesenchymal transition by downregulating the Wnt signaling pathway and upregulating NKD2 expression in colon cancer cells

Oncol Rep. 2016 May;35(5):2615-23. doi: 10.3892/or.2016.4669. Epub 2016 Mar 10.

Abstract

Tumor invasion and metastasis are closely associated with epithelial‑mesenchymal transition (EMT). EMT refers to epithelial cells under physiological and pathological conditions that are specific to mesenchymal transition. Curcumin inhibits EMT progression via Wnt signaling. The Wnt signaling pathway is a conservative EMT‑related signaling pathway that is involved in the development of various tumors. In the present study, MTS assays were employed to analyze the proliferation of curcumin‑treated cells. Naked cuticle homolog 2 (NKD2), chemokine receptor 4 (CXCR4) and antibodies associated with EMT were examined in SW620 colorectal cancer cell lines using western blot analysis and real‑time qPCR. NKD2 small‑interfering RNA (siRNA) and CXCR4 expression plasmid was synthesized and transfected into the colorectal cancer cell lines, and NKD2 and CXCR4 expression levels were detected. The results showed that curcumin significantly inhibited the proliferation of colorectal cancer cells and upregulated the expression of NKD2 in SW620 colorectal cancer cells and in the xenograft, resulting in the downregulation of key markers in the Wnt signaling. In addition, the progression of ETM was inhibited due to the overexpression of E‑cadherin as well as the downregulation of vimentin. Curcumin also inhibited tumor metastasis by downregulating the expression of CXCR4 significantly. The results suggested involvement of the NKD2‑Wnt‑CXCR4 signaling pathway in colorectal cancer cells. In addition, curcumin is inhibit this signaling and the development of colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents / pharmacology*
  • Calcium-Binding Proteins
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Curcumin / pharmacology*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Up-Regulation
  • Wnt Signaling Pathway*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • CXCR4 protein, human
  • Calcium-Binding Proteins
  • Carrier Proteins
  • NKD2 protein, human
  • Receptors, CXCR4
  • Curcumin