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 E2 (PGE2) 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 PGE2, a combination of PGE2 and c-fos antisense oligodeoxynucleotide (ASO), and PGE2 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 PGE2 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 PGE2 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 PGE2 treatment, which was significantly higher than that at 0 h (33.2+/-2.4%, P<0.01). C-fos ASO significantly reduced PGE2-induced VEGF mRNA expression in HepG2 cells.

Conclusion: PGE2 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.