title: MDA-7/IL-24 suppresses tumor adhesion and invasive potential in hepatocellular carcinoma cell lines.
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.
authors.affiliation: Department of Medical Oncology, Dalian Municipal Central Hospital, Dalian, Liaoning 116033, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huo
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Li
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Zhu
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Bao
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: An
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D016195:G2 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D056945:Hep G2 Cells; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics; D009361:Neoplasm Invasiveness; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000235:genetics; D000099180:Interleukin-24
chemical_list: D007378:Interleukins; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D000099180:Interleukin-24