CXCL8 induces epithelial-mesenchymal transition in colon cancer cells via the PI3K/Akt/NF-κB signaling pathway

Shen,Tao; Yang,Zhibin; Cheng,Xianshuo; Xiao,Youchuan; Yu,Kun; Cai,Xinyi; Xia,Cuifeng; Li,Yunfeng

doi:10.3892/or.2017.5453

CXCL8 induces epithelial-mesenchymal transition in colon cancer cells via the PI3K/Akt/NF-κB signaling pathway

Authors:
- Tao Shen
- Zhibin Yang
- Xianshuo Cheng
- Youchuan Xiao
- Kun Yu
- Xinyi Cai
- Cuifeng Xia
- Yunfeng Li
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Affiliations: Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China, Department of Oncology, Qujing First People's Hospital of Yunnan Province, Qujing, Yunnan 655000, P.R. China
Published online on: February 14, 2017 https://doi.org/10.3892/or.2017.5453
Pages: 2095-2100

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Abstract

The aim of the present study was to investigate the role of chemokine (C-X-C motif) ligand 8 (CXCL8) in the proliferation, invasiveness and metastasis of colon cancer and its role in the induction of epithelial-mesenchymal transition (EMT) via activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-κB (NF-κB) pathway. The plasmid vector containing CXCL8 cDNA was transfected into LoVo cells using Lipofectamine 2000 reagent. Real-time PCR and western blot analyses were performed to determine expression of CXCL8. MTT growth inhibition, scratch and Transwell invasion assays were conducted to assess cell proliferation, migration and invasiveness of the CXCL8-transfected LoVo cells. Western blot analyses were conducted to measure the levels of phosphorylation of protein in the PI3K/Akt/NF-κB pathway in the CXCL8-transfected LoVo cells. Expression levels of CXCL8 mRNA and protein were significantly increased in the CXCL8-transfected LoVo cells compared with levels in the control and empty-vector cells (P<0.05). Overexpression of CXCL8 increased proliferation of the LoVo cells and significant differences in cell viability were observed 48 h after transfection (P<0.05) and remained significant at 72 and 96 h. CXCL8-transfected LoVo cells had a significantly higher migration rate and doubled invasion. The CXCL8-transfected LoVo cells exhibited an EMT-like phenotype, compared with control and empty-vector cells, with decreased expression of E-cadherin accompanied by increased expression of N-cadherin, vimentin and α-SMA. Overexpression of CXCL8 activated the PI3K/Akt/NF-κB pathway by promoting the phosphorylation of PI3K, Akt and NF-κB. Subcutaneous tumors were generated by subcutaneous injection of LoVo parental cells or CXCL8-transfected LoVo cells in BALB/c nude mice. The tumor growth was more rapid in the CXCL8-transfected group than that noted in the parental cell group. In conclusion, overexpression of CXCL8 induced cell proliferation, migration and invasion of colon cancer LoVo cells. CXCL8 may act through induction of EMT via the PI3K/AKT/NF-κB signaling axis.

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