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Indexed by:期刊论文

Date of Publication:2013-08-01

Journal:ONCOLOGY REPORTS

Included Journals:SCIE、Scopus

Volume:30

Issue:2

Page Number:986-992

ISSN No.:1021-335X

Key Words:human hepatocellular carcinoma; MDA-7/IL-24; tumor metastasis

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-beta, and a reporter gene assay was used to detected the transcriptional activity of NF-kappa B 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-beta and p-Akt, transcriptional activity of NF-kappa B, 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.