Experimental Study Of The Effect Of Somatostatin Analog Octreotide On The Expression And Production Of VEGF In Human Hepatocellular Carcinoma Cells

Hepatic carcinoma is one of the most common malignancies in China, comprehensive treatment play an important role for inoperative hepatic carcinoma. Somatostatin analog octreotide has been recently suggested to inhibit experiment angiogenesis and suppress tumor growth through inhibition of angiogenesis. We had previously demonstrated that octreotide could inhibit angiogenesis induced by HCC and might be an antitumor angiogenic compound. However, the exact mechanism of the anti-angiogenesis effect of octreotide on HCC has not been elucidated. Hepatocellular carcinoma (HCC) is generally considered to be a hypervascular solid tumor. Tumor cells can produce several angiogenic factors, including vascular endothelial growth factor (VEGF) that is the most important angiogenic factor. VEGF plays a key role for the development of angiogenesis and has relation to the growth, recurrence and metastasis of HCC. To investigate the effect of somatostatin analogue octreotide on the expression and production of VEGF and intracelluar signal transduction in HCC cells line BEL-7402 and explore its antitumor angiogenic mechanism. BEL-7402 HCC cell line was used in this study. The effects of octreotide on basic and growth factors (EGF/ bFGF)-stimulated VEGF mRNA expression, and intracellular protein production and secretion in HCC cells were measured by RT-PCR, flow cytometry and enzyme linked immunosorbant assay (ELISA) respectively. The cell DNA content was detected by fluorescence activated flow cytometry analysis, and the c-Fos and extracellular singal-regulated protein kinase (ERK) protein expression levels were detected byimmunblotting. The present study demonstrates that octreotide in concentrations from 10-5mol/L to 10-7 mol/L inhibits VEGF mRNA expression, intracellular production and secretion of VEGF of HCC cells line BEL-7402; but octreotide in concentrations less than 10-7mol/L can gently increased VEGF mRNA expression, intracellular production and secretion of VEGF. Apoptosis was not induced when HCC cells were treated with octreotide. Octreotide in concentrations 10"5 mol/L could significantly inhibit VEGF mRNA expression, intracellular production and secretion of VEGF stimulated by growth factors. The basic and stimulated c-Fos and ERK-l/ERK-2 proteins were decreased in HCC BEL-7402 cells that treated with octreotide by immunblotting analysis. These results suggest that octreotide inhibits ERK-l/ERK-2 and c-Fos expression and interferes with transcription factor AP-1 formation, which result in inhibition to expression and production of VEGF in HCC cells. Octreotide may be an antitumor angiogenic compound through inhibiting the expression and production of VEGF in HCC cells.