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目的探讨促血管生成素(Ang)及其受体Tie-2在胃癌中的表达及其与胃癌血管生成的关系。方法应用RT-PCR和免疫组化分析技术,检测68例胃癌组织及其相应的癌旁胃黏膜Ang-1、Ang-2及Tie-2mRNA和蛋白表达水平,计数微血管密度(MVD)。结果胃癌组织及相应癌旁组织均见Ang-1、Ang-2及Tie-2mRNA的表达,Ang-1蛋白、Tie-2mRNA表达水平与MVD呈负相关(r=-0.440,r=-0.267;P<0.05),Ang-2mRNA及蛋白表达水平与MVD呈正相关(r=0.319,r=0.729;P<0.05),Ang-2/Ang-1蛋白表达的比值与MVD呈正相关(r=0.739,P<0.05)。在Ang-2mRNAT/N比值(胃癌与癌旁胃粘膜mRNA表达水平的比值)>1.2时,其MVD均高于T/N比值<1.2者,而与Ang-1mRNA的表达情况无关。结论Ang-1与Ang-2蛋白在胃癌血管生成中相互拮抗,Ang-2/Ang-1的比值可能是决定胃癌血管生成和肿瘤生长的最终因素。当Ang-2高表达而Ang-1低表达时,促进胃癌的血管生成;反之,则抑制胃癌血管生成。推测Angs及其受体系统在胃癌血管生成中的调节作用是以Ang-2的作用为主导的。
Objective To investigate the expression of angiopoietin (Ang) and its receptor Tie-2 in gastric cancer and its relationship with angiogenesis in gastric cancer. Methods RT-PCR and immunohistochemical techniques were used to detect the mRNA and protein expression of Ang-1, Ang-2 and Tie-2 in 68 specimens of gastric carcinoma and their corresponding adjacent gastric mucosa, and to count the microvessel density (MVD). Results The expressions of Ang-1, Ang-2 and Tie-2 mRNA were detected in gastric cancer tissues and their adjacent tissues. The expression of Ang-1 protein and Tie-2 mRNA was negatively correlated with MVD (r=-0.440, r=-0.267; P<0.05), Ang-2 mRNA and protein expression levels were positively correlated with MVD (r=0.319, r=0.729; P<0.05), and the ratio of Ang-2/Ang-1 protein expression was positively correlated with MVD (r=0.739, P<0.05). The MVD of Ang-2 mRNA T/N ratio (ratio of gastric cancer and para-cancerous gastric mucosal mRNA expression)>1.2 was higher than that of T/N ratio<1.2, but not Ang-1 mRNA expression. Conclusions Ang-1 and Ang-2 proteins antagonize each other in angiogenesis of gastric cancer, and the ratio of Ang-2 to Ang-1 may be the ultimate factor in determining angiogenesis and tumor growth in gastric cancer. When Ang-2 is highly expressed and Ang-1 is lowly expressed, angiogenesis is promoted in gastric cancer; conversely, angiogenesis is inhibited in gastric cancer. It is speculated that the regulation of Angs and its receptor system in angiogenesis of gastric cancer is based on the role of Ang-2.