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

Zhang,Zewei; Chen,Haitao; Xu,Chao; Song,Lu; Huang,Lulu; Lai,Yuebiao; Wang,Yuqi; Chen,Hanlu; Gu,Danlin; Ren,Lili; Yao,Qinghua

doi:10.3892/or.2016.4669

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

Authors:
- Zewei Zhang
- Haitao Chen
- Chao Xu
- Lu Song
- Lulu Huang
- Yuebiao Lai
- Yuqi Wang
- Hanlu Chen
- Danlin Gu
- Lili Ren
- Qinghua Yao
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Affiliations: Department of Abdominal Surgical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, Second Clinical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, First Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of Integrated Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
Published online on: March 10, 2016 https://doi.org/10.3892/or.2016.4669
Pages: 2615-2623
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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