环氧合酶-2、核因子(-K)_B在胃癌、癌前病变中的表达及尼美舒利逆转其表达的实验研究

The significance of the expression of COX-2 and NF-κB in gastric atypical hyperplasia and gastric cancer and the inhibitory effects of nimesulide on these expressions in human gastric carcinoma cell line SGC-7901

目的探讨环氧合酶(COX)-2、核因子(NF)-kB 在胃癌及异型增生中的表达,并研究尼美舒利对人胃癌 SGC-7901细胞增殖及 COX-2、NF-kB 表达的影响。方法采用免疫组化 Power vi-sionTM 两步法对84例胃癌和54例胃异型增生组织中 COX-2、NF-kB 的表达进行检测;在体外实验中对人胃癌 SGC-7901细胞采用细胞培养,MTT 法检测不同浓度尼美舒利对人胃癌 SGC-7901细胞增殖的抑制作用,免疫组化、Western blot 方法检测药物对 COX-2、NF-kB 表达的影响。结果 COX-2、NF-kB 在胃癌中的阳性表达率分别为66.67%、59.52%,均高于异型增生(P<0.05),COX-2表达与肿瘤的大小、淋巴转移呈正相关(P<0.05),并与 NF-kB 的表达相关(P<0.05),COX-2与肿瘤浸润深度正相关(P<0.05)。体外实验中结果显示尼美舒利可以抑制人胃癌 SGC-7901细胞生长并具有浓度、时间依赖性;与阴性对照组相比,药物作用48 h 后尼美舒利100、200μmol/L 组 COX-2、NF-kB 蛋白表达明显减弱并具有剂量依赖性(P<0.05),COX-2、NF-kB 之间正相关(P<0.05)。结论 COX-2、NF-kB与胃癌的发生转移相关,并且 NF-kB 蛋白作为上游调控因子调节 COX-2的表达。尼美舒利可以抑制人胃癌 SGC-7901细胞增殖,抑制 COX-2、NF-kB 的表达在其抑制肿瘤机制中可能具有一定作用。

Objective To explore the expression and the relationship of cyclooxygenase 2 （COX-2） and nuclear factor-κB（NF-κB） protein in gastric cancer and atypical hyperplasia and to investigate the inhibitory effects of nimesulide on cell proliferation and COX-2, NF-κB expression in human gastric carcinoma cells. Methods The expressions of COX-2, NF-κB were determined with Power visionTM immunohistochemical analysis in 84 gastric cancers and 54 gastric atypical hyperplasia. SGC-7901 cells were treated by nimesulide. The anti-proliferative effect was measured by using MTT assay; the expressions of COX-2 and NF-κB were examined by immunohistochemical stain and western-blot analysis. Results Positive rates of COX-2 （66. 67% ） , NF-κB（ 59.52% ）in gastric cancer were significantly higher than those in gastric atypical hyperplasia （P 〈0. 05）. Over expression of COX-2 in gastric cancer was related to lymph node metastasis and tumor size （ P 〈 0. 05 ）. There was correlation between the expression of COX-2 and NF-κB. And the expression of COX-2 was positively related to invasion of gastric cancer. SGC-7901 cells proliferation was inhibited by treatment of nimesulide in close and time dependent manner. The expression of COX-2, NF-κB in 100,200 μmol/L nimesulide groups were significantly decreased than that in control group（P 〈 0.05 ）. There was positive correlation between the expression of COX-2 and NF-κB （ P 〈 0. 05 ）. Conclusion The expression of COX-2 ,NF-κB may play an important role in the occurrence and progress of gastric cancer . The proliferation of SGC-7901 cell was inhibited after treated by nimesulide . Suppressing COX-2 and NF-κB expressions may play some roles in the antitumor process.