Effect of c-fos antisense probe on prostaglandin E2-induced upregulation of vascular endothelial growth factor mRNA in human liver cancer cells

AIM: To examine the effect of prostaglandin E-2 (PGE(2)) on the expression of vascular endothelial growth factor (VEGF) mRNA in the human hepatocellular carcinoma (HCC) HepG2 cells and the possible involvement of c-fos protein in this process. METHODS: Human HCC HepG2 cells were divided into three groups treated respectively with PGE(2), a combination of PGE(2) and c-fos antisense oligodeoxynucleotide (ASO), and PGE(2) plus c-fos sense oligodeoxynucleotide (SO). The expression of VEGF mRNA in HepG2 cells after different treatments was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The relative expression level of VEGF mRNA in HepG2 cells in each group was measured. RESULTS: Administration of PGE(2) resulted in an increased expression of c-fos and VEGF mRNA in HepG2 cells. The relative expression level of c-fos mRNA reached the peak at 3 h (68.4 +/- 4.7%) after PGE(2) treatment, which was significantly higher than that at 0 h (20.6 +/- 1.7%, P<0.01). Whereas, the highest expression level of VEGF mRNA was observed at 6 h (100.5 +/- 6.1%) after PGE(2) treatment, which was significantly higher than that at 0 h (33.2 +/- 2.4%, P<0.01). C-fos ASO significantly reduced PGE(2)-induced VEGF mRNA expression in HepG2 cells. CONCLUSION: PGE(2) increases the expression and secretion of VEGF in HCC cells by activating the transcription factor c-fos, promotes the angiogenesis of HCC and plays an important role in the pathogenesis of liver cancer. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.