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目的 研究血管内皮生长因子 (VEGF)和基质金属蛋白酶 9(MMP 9)的表达与食管癌血管形成和临床的关系 ,以及低氧对其的调节作用。方法 用逆转录 聚合酶链式反应 (RT PCR)检测了42例食管癌手术标本 (包括 18例癌旁组织 )中VEGF和MMP 9mRNA的表达 ,用免疫组化染色的方法检测了 5 6例食管癌标本中VEGF蛋白的表达和平均血管密度 (MVD) ,同时用酶联免疫吸附试验(ELISA)的方法定量测定了低氧对食管癌细胞系中VEGF和MMP 9表达的影响。结果 食管癌中VEGF的表达显著高于癌旁组织 ,与肿瘤内平均MVD密切正相关 ,VEGF表达和肿瘤中MVD计数与食管癌的分期、淋巴结转移密切相关。食管癌中MMP 9的表达也显著高于癌旁组织 ,但MMP 9的表达与食管癌中的MVD计数和临床病理特征无关。低氧可以显著增加食管癌细胞系中VEGF的表达 ,但对MMP 9的表达无明显影响。结论 VEGF的表达可能在食管癌血管形成和转移中起重要作用 ,并受低氧调节 ,有可能作为反映食管癌进展的生物学指标和抗血管治疗的靶点。
Objective To investigate the relationship between the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP 9) and the angiogenesis and clinical status of esophageal carcinoma and the regulation by hypoxia. Methods RT-PCR was used to detect the expression of VEGF and MMP 9 mRNA in 42 cases of esophageal cancer specimens (including 18 cases of paracancerous tissues). The expressions of VEGF and MMP 9 mRNA in esophageal cancer tissues were detected by immunohistochemical staining The expression of VEGF protein and mean vessel density (MVD) in cancer specimens were detected by enzyme-linked immunosorbent assay (ELISA). The effect of hypoxia on the expression of VEGF and MMP 9 in esophageal cancer cell lines was quantified. Results The expression of VEGF in esophageal cancer was significantly higher than that in paracancerous tissues, which was positively correlated with the mean MVD in tumor. The expression of VEGF and the MVD in esophageal cancer were closely related to the stage of esophageal cancer and lymph node metastasis. The expression of MMP 9 in esophageal cancer was also significantly higher than that in paracancerous tissues, but the expression of MMP 9 was not related to MVD count and clinicopathological features in esophageal cancer. Hypoxia could significantly increase the expression of VEGF in esophageal cancer cell lines, but had no significant effect on the expression of MMP-9. Conclusion The expression of VEGF may play an important role in angiogenesis and metastasis of esophageal cancer and is regulated by hypoxia. It may be used as a biological target to reflect the progress of esophageal cancer and the target of anti-angiogenesis.