环氧合酶-2对胃癌淋巴管形成的影响

The effect of cyclooxygenase-2 on lymphangiogenesis and prognosis in Gastric cancer

目的探讨环氧合酶-2(COX-2)对胃癌淋巴管形成及预后的关系。方法2004年2月-2004年10月临床资料完整的手术切除的并经病理证实的胃癌患者63例,采用免疫组化方法检测63例胃癌组织中COX-2、VEGF-C、受体VEGFR-3的表达及微淋巴管密度(MLD)。逆转录聚合酶链式反应(RT-PCR)检测人胃癌细胞SGC-7901分别加入不同浓度的COX-2抑制剂尼美舒利与加入外源性前列腺素E2(PGE2)后VEGF-CmRNA及蛋白的变化。结果63例胃癌石蜡标本中COX-2、VEGF-C阳性表达率为77.6%、72.9%。COX-2与VEGF-C、淋巴管密度、淋巴结转移呈正相关(P<0.01)。COX-2与胃癌生存率呈负相关,COX-2表达阴性组5年生存率显著高于其表达阳性组(P<0.05)。尼美舒利以剂量依赖性方式下调VEGF-CmRNA表达,而PGE2以剂量依赖性方式上调VEGF-CmRNA表达。结论COX-2可能通过上调VEGF-C的表达,促进胃癌的淋巴管形成和淋巴结转移,并影响胃癌患者的预后。

Objective To study the effect of cyclooxygenase-2（COX-2） in gastric cancer and the correlation with lymph anglo- genesis and prognosis. Methods Sixty-three gastric cancer samples were tested with using immunohistochemistry COX-2, Vascular endothelial growth factor-C （VEGF-C） and VEGFR-3 were examined.The expressions of VEGF-C mRNA and protein were detected by reverse transcription-polymerase chain reaction （RT-PCR） and Western blot in SGC-7901 cell lines by the treatment of selective COX-2 inhibitor Nimesalide at different doses. The expressions of VEGF-C protein were evaluated in SGC-7901 cells treated by PGE2 respectively. Results The positive rate of COX-2 and VEGF-C in 63 gastric cancer samples was77.6% and 72.9% respectively. both significantly higher than those in non-cancerous gastric mucosa. COX-2 was positively correlated with VEGF-C（ P 〈 0.01 ）, lym- phatic vessels density（ P = 0. 032 ） and lymph node metastasis （P = 0.041 ）. COX-2 expression was negatively Correlated with a 5-year survival rate. The 5-year survival of patients with negative COX-2 expression was significantly higher compared to that with positive COX-2 expression （P 〈 0.01 ）. Nimesulide could down-regulate the expressions of VEGF-C and protein in adoes-dependent manner, the expressions of VEGF-C protein up-regulated by PGE-2 treatment. Conclusion COX-2 over-expression can up-regulate the pression of VEGF-C. correlated with VEGF-C （ P 〈 0.01 ）, b^nphatic vessels density （ P = O. 032） and VEGF-C might promote lymph node metastasis by a lymphangiogenic pathway, than affect the prognosis of the patients with gastric cancer.