MDA-7/IL-24 suppresses tumor adhesion and invasive potential in hepatocellular carcinoma cell lines

Huo,Wei; Li,Zhi-Min; Zhu,Xiao-Min; Bao,Yong-Ming; An,Li-Jia

doi:10.3892/or.2013.2507

MDA-7/IL-24 suppresses tumor adhesion and invasive potential in hepatocellular carcinoma cell lines

Authors:
- Wei Huo
- Zhi-Min Li
- Xiao-Min Zhu
- Yong-Ming Bao
- Li-Jia An
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Affiliations: Department of Medical Oncology, Dalian Municipal Central Hospital, Dalian, Liaoning 116033, P.R. China, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024, P.R. China
Published online on: May 29, 2013 https://doi.org/10.3892/or.2013.2507
Pages: 986-992

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Abstract

Melanoma differentiation associated gene-7 (MDA-7)/interleukin‑24 (IL-24) has been considered as a tumor-suppressor gene, which suppresses the growth and induces the apoptosis of cancer cells. In the present study, we investigated the effect and mechanisms of MDA-7/IL-24 regarding the inhibition of metastasis of HepG2 and BEL-7402 human hepatocellular carcinoma (HCC) cells in vitro. We established MDA-7/IL-24-overexpressing HepG2 and BEL-7402 cell lines and found that MDA-7/IL-24 overexpression inhibited tumor cell adhesion and invasion, and induced G2/M arrest in tumor cells. To explore its mechanism of action, western blotting and real-time-PCR assay were used to investigate the expression of E-cadherin, CD44, ICAM-1, matrix metalloproteinase (MMP)-2 and -9, CyclinB, Twist, survivin, p-ERK and p-Akt. ELISA assay was used to measure the secretion of TGF-β, and a reporter gene assay was used to detected the transcriptional activity of NF-κB and AP-1 in HepG2 and BEL-7402 cells. The results showed that MDA-7/IL-24 overexpression decreased the expression of CD44, ICAM-1, MMP-2/-9, CyclinB, Twist, survivin, TGF-β and p-Akt, transcriptional activity of NF-κB, and increased the expression of E-cadherin and p-ERK and transcriptional activity of AP-1 in HepG2 and BEL-7402 cells. Our results revealed that MDA-7/IL-24 mediated the inhibition of adhesion and invasion in HepG2 and BEL-7402 cells by suppressing metastasis-related gene expression. Thus, MDA-7/IL-24 may be used as a novel cancer-suppressor gene for the therapy of human HCC.

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