Murata H, Kawano S, Tsuji S, Tsuji M, Sawaoka H, Kimura Y, Shiozaki H, Hori M
First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
Am J Gastroenterol. 1999 Feb;94(2):451-5. doi: 10.1111/j.1572-0241.1999.876_e.x.
Recent epidemiological studies indicate that there is reduced risk of all digestive carcinomas in patients who regularly take nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin. Cyclooxygenase (COX) is a target enzyme for NSAIDs. We investigated the role of two isoforms, COX-1 and COX-2, in the development and metastasis of gastric carcinoma.
Fifteen gastric carcinoma tissue specimens and accompanying adjacent mucosa specimens were obtained from surgical resections. COX-1 and COX-2 protein expression were evaluated using Western blotting analysis, and their relative band densities were semi quantified using standard densitometry scanning techniques.
Compared with paired noncancerous specimens, COX-2 was overexpressed in 10 of 15 carcinoma tissue specimens (66.7%). Overall, COX-2 levels in carcinoma tissue were significantly higher. Two early carcinomas (confined to the mucosa and submucosa) and three of 13 advanced carcinomas (extended below the submucosa into the muscular wall) had weak or similar COX-2 expression in paired tissue specimens. COX-2 overexpression in tumors significantly correlated with tumor invasion into the lymphatic vessels in the gastric wall and metastasis to the lymph nodes. Furthermore, the stage grouping in the TNM classification significantly correlated with COX-2 overexpression. In contrast, COX-2 overexpression did not correlate with histopathological grading, surface size, and venous vessel invasion of the tumors. COX-1 levels were similar between paired tissues.
COX-2 overexpression might enhance lymphatic invasion and metastasis in patients with gastric carcinoma, implicating a poor prognosis. Therefore, the use of COX-2-specific inhibitor to suppress lymphatic metastasis in humans should be investigated.
近期的流行病学研究表明，定期服用阿司匹林等非甾体抗炎药（NSAIDs）的患者患所有消化系统癌症的风险降低。环氧化酶（COX）是非甾体抗炎药的靶酶。我们研究了两种同工型COX-1和COX-2在胃癌发生和转移中的作用。
从手术切除标本中获取15份胃癌组织标本及其相应的相邻黏膜标本。采用蛋白质印迹分析评估COX-1和COX-2蛋白表达，并使用标准光密度扫描技术对其相对条带密度进行半定量分析。
与配对的癌旁标本相比，15份癌组织标本中有10份（66.7%）COX-2过表达。总体而言，癌组织中的COX-2水平显著更高。在配对组织标本中，2例早期癌（局限于黏膜和黏膜下层）和13例进展期癌中的3例（延伸至黏膜下层以下进入肌层）COX-2表达较弱或相似。肿瘤中COX-2过表达与肿瘤侵犯胃壁淋巴管及淋巴结转移显著相关。此外，TNM分类中的分期分组与COX-2过表达显著相关。相比之下，COX-2过表达与肿瘤的组织病理学分级、表面大小及静脉侵犯无关。配对组织间COX-1水平相似。
COX-2过表达可能增强胃癌患者的淋巴侵袭和转移，提示预后不良。因此，应研究使用COX-2特异性抑制剂抑制人类淋巴转移。
