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Objective To investigate the expressions of PGE2 and COX-2 between colorectal cancer tissue and normal colorectal mucosa tissue,and its relation to clinical pathology and significance.Methods 115 colon cancerous tissues and 69 normal colon tissues were collected in our hospital from Jan 2010 to Sept 2011.Immunohistochemistry was used to detect the PGE2 and COX-2 expression in both of the colorectal cancer and normal tissues.Results Positive expressions of PGE2 and COX-2 were 87.8％ (101/115) and 80.9％ (93/115) in the colorectal cancer tissue,and 8.7％ (6/69),21.7％ (15/69) in normal colorectal mucosa tissue respectively (x2 =110.96,62.194,all P ＜ 0.05).Expressions of PGE2 and COX-2 were closely associated with,tumor invasion,differentiation,lymph node metastasis and TNM stage (P ＜ 0.05).The Spearman rank correlation analysis indicated that the PGE2 and COX-2 expressions in tissues were closely correlated (r =0.987,P ＜ 0.05).Survival rate of the patients in both negative expressions of PGE2 and COX-2 (63.6％) were higher than that of both positive expressions (37.8％,P ＜ 0.05).Conclusion High PGE2 and COX-2 expressions in colorectal cancer tissues predicts poor patients' survival.
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Objective To investigate the effect of CXCL12 on the secretion of CXCL8 from colon cancer cells and the mechanism of co-regulation of proliferation and metastasis of colon cancer.Methods The expression levels of CXCL8 and CXCl12 in 5 human colon cancer cell lines (DLD-1,HT29,WiDr,CaCo-2,Colo320),fibroblasts,and human umbilical vein endothelial cells (HUVEC) were studied by Western blotting,respectively.ELISA,proliferation and invasion assay were used to explore the role of CXCL12 and CXCL8 for metastatic process of colon cancer and interaction between colon cancer cell and stromal cell in the microenvironment,respectively.Results The expression of CXCL8 was detected in all colon cancer cell lines,fibroblasts and HUVEC,while CXCL12 was expressed only in DLD-1 cell and fibroblast.The secretion level of CXCL8 in CaCo-2,WiDr,HT-29 and HUVEC (2.54-fold vs.control,2.07-fold vs.control,1.87-fold vs.control,2.79-fold vs.control) was enhanced by CXCL12 that derived from fibroblasts(P ＜ 0.01).CXCL8 could significantly promote the proliferation,migration of HUVEC (P ＜0.01).CXCL8 and CXCL12 enhanced proliferation of HUVEC (P ＜ 0.01),invasion of HUVEC and HT-29 (P ＜ 0.01) in a concentration-dependent manner.Conclusion Fibroblasts derived CXCL12 enhanced the CXCL8 secretion in colon cancer cells,and CXCL8 and CXCL12 can promote the proliferation and invasion of colon cancer cells.
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<p><b>OBJECTIVE</b>To investigate the effects of polyunsaturated fatty acids (PUFA) ω-3 and ω-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.</p><p><b>METHODS</b>The effects of ω-3, ω-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell (HUVEC) were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of ω-3, ω-6, PGE2 and PGE3 on neovascularization. In all the assays, groups without ω-3, ω-6, PGE2 and PGE3 were designed as the control.</p><p><b>RESULTS</b>With the increased concentration of ω-6 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs enhanced, and the number of migration cells also increased from 28.2±3.0 to 32.8±2.1, which was higher than control group (21.2±3.2) respectively (both P<0.05). With the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs was inhibited, and the number of migration cells decreased from 15.8±2.0 to 11.0±2.1, which was lower than control group (22.1±3.0) respectively (both P<0.05). In the angiogenesis assay, compared with control group (standard number: 43 721±4 654), the angiogenesis ability of HUVECs was significantly enhanced by ω-6 in concentration-dependent manner (1 μmol/L group: 63 238±4 795, 10 μmol/L group: 78 166±6 123, all P<0.01). Meanwhile, with the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the angiogenesis ability was significantly decreased from 30 129±3 102 to 20 012±1 541(all P<0.01). The proliferation and migration ability of HUVECs were significantly promoted by ω-6 metabolites PGE2 (P<0.05) in a concentration-dependent manner. In contrast, ω-3 metabolites PGE3 significantly inhibited the proliferation and migration ability of HUVECs in a concentration-dependent manner (all P<0.05). After rofecoxib (a COX-2 specific inhibitor) inhibited the expression of COX-2, the expression level of PGE2 was significantly decreased in a dose-dependent manner. In co-culture system, whose gastric cancer cells expressed positive COX-2, ω-6 could increase angiogenesis of gastric cancer cells(P<0.01), but ω-3 could inhibit such angiogenesis(P<0.01). In co-culture system, whose gastric cancer cells did not express COX-2, ω-3 could inhibit the angiogenesis of gastric cancer cells (P<0.05), but ω-6 had no effect on angiogenesis.</p><p><b>CONCLUSIONS</b>The PUFA ω-6 can enhance the angiogenesis via the promotion of proliferation and migration of HUVECs, and COX-2 and PGE2 may play an important role in this process, whereas, the ω-3 can inhibit the angiogenesis through its middle metabolites PGE3 to inhibit the proliferation and migration of HUVECs. Results of this experiment may provide a new approach to inhibit and prevent the spread of gastric cancer.</p>