کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4302698 | 1288461 | 2010 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Down-Regulation of c-Met Expression Inhibits Human HCC Cells Growth and Invasion by RNA Interference Down-Regulation of c-Met Expression Inhibits Human HCC Cells Growth and Invasion by RNA Interference](/preview/png/4302698.png)
BackgroundCell migration is a basis for invasion and metastasis of malignant tumors. Receptor tyrosine kinases are recognized as important therapeutic targets in antineoplastic strategies. C-met is a receptor tyrosine kinase highly expressed in human hepatocellular carcinoma (HCC) cell line MHCC97-H. Higher expression of c-met in tumor tissue can lead to scattering, angiogenesis, proliferation, enhanced cell motility, invasion, and eventually, metastasis. To explore the roles of c-met in modulating the motility of cell, we silenced c-met expression in the HCC line MHCC97-H by RNA interference (RNAi).Materials and MethodsFor transient expression, c-met-siRNA 1,2 recombinant plasmids were transfected into phoenix A cells. The MHCC97-H cells were cultured in Dulbecco's modified Eagles's medium (DMEM) with 10% fetal bovine serum (FBS) to establish MHCC97-H HCC cells stably expressing c-met-siRNA. MHCC97-H cells were treated with the recombinant virus for assay of c-met mRNA and protein, evaluation of growth and invasion of MHCC97-H cells, and identification of hepatitis B virus X (HBX) protein correlation with c-met.ResultsAfter transfection of c-met-siRNA for 48 h, the expression of c-met decreased markedly in MHCC97-H cells; the most effective site of the siRNA target sequence is at the 537 upstream, far from the transcription start. In addition, the proliferation, motility, and invasive ability of MHCC97-H cells were significantly inhibited. Furthermore, we showed that hepatitis B virus (HBV) X protein (HBX) potentiated the activities of the extracellular signal-regulated kinase 1/2 (ERK1/2) in MHCC97-H cells. Treatment with extracellular signal-regulated kinase (ERK) inhibitor (U0126), but not P38 MAPK inhibitor (SB203580) or phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin), markedly suppressed the expression of c-met protein in MHCC97-H cells.ConclusionThese results indicate that the over-expression of c-met protein plays an important role in the cell invasion of MHCC97-H, and HBX protein may promote the expression of c-met by ERKs pathway.
Journal: Journal of Surgical Research - Volume 162, Issue 2, August 2010, Pages 231–238