Antiproliferative and proapoptotic effects of somatostatin on activated hepatic stellate cells

AIM: To assess the effects of somatostatin on proliferation and apoptosis of activated rat hepatic stellate cells (HSCs). METHODS: HSCs isolated from the livers of adult SpragueDawley rats (weighing 400-500 g) by in situ perfusion and purified by single-step density gradient centrifugation with Nycodenz, became activated after 10 days' cultivation. Then the apoptotic rate of HSCs treated with different doses of somatostatin for 72 h, was assayed by acridine orange/ethidium bromide fluorescent staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, transmission electron microscopy and flow cytometry, while the proliferation of HSCs was measured by MTT assay. Furthermore, the mechanisms of somatostatin were investigated by cytodynamic analysis. RESULTS: Somatostatin at the concentration of 10^-6-10^-99 mol/L could decrease the proliferative rate, and promote the apoptosis of activated rat HSCs in a dose-dependent way. Its action was most significant when the concentration reached 10^-6 mol/L or 10^-7 mol/L (P<0.05-0.01). An obvious cell-cycle arrest (G0/G1 arrest) was the important way for somatostatin to exert its action. CONCLUSION: Antiproliferative and proapoptotic effects of low-dose somatostatin on activated rat HSCs can be obtained. These findings reveal its potential antifibrotic action.

Mechanism and clinical significance of cyclooxygenase-2 expression in gastric cancer

AIM: To determine the correlation between methylation status of 5' CpG island of cyclooxygenase-2 (COX-2) gene and protein expression in gastric cancer tissues for distinguishing the molecular characters of gastric cancers. METHODS: Methylation status of 5' CpG island of COX-2 gene was studied by PCR amplification after HpaⅡ and Hha I restrictive enzyme digestion;COX-2 expression was evaluated by immunohistochemical method. RESULTS: Hpa Ⅱ and HhaI site were all methylated in 12 normal gastric mucosa tissues, whereas they were demethylated in 77.27% (34/44) and 84.09% (37/44) gastric cancer tissues,respectively.Expression of COX-2 was detected in 68.18% (30/44) gastric cancer tissues, but no expression was found in normal gastric mucosa tissues. In gastric cancer tissues, COX-2 expression was correlated significantly with HpaⅡ site demethylation (29/30 vs 5/14, P<0.001 and HhaI site demethylation (28/30 vs 9/14,P<0.05). CONCLUSION: The demethylation of 5' CpG island of gene is necessary for COX-2 expression in human gastric cancer. The expression status of COX-2 may provide theoretical basis for COX-2 targeting gastric cancer treatments.