Zimmermann K C, Sarbia M, Weber A A, Borchard F, Gabbert H E, Schrör K
Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Cancer Res. 1999 Jan 1;59(1):198-204.
On the basis of epidemiological observations that nonsteroidal antiinflammatory drugs reduce the risk of esophageal carcinoma, we studied the expression of cyclooxygenase-2 (COX-2) in esophageal squamous cell carcinomas (SCCs; n = 172) and in esophageal adenocarcinomas (ADCs; n = 27). Using immunohistochemistry, we observed COX-2 expression in 91% of the SCCs and in 78% of the ADCs. Western blot analysis showed enhanced expression of the COX-2 protein in some tumors as compared with normal esophageal squamous epithelium, whereas similar amounts of the COX-1 protein were found in normal and cancerous tissues. COX expression was also studied in two esophageal cancer cell lines (OSC-1 and OSC-2) to evaluate the functional relevance of COX-2-derived prostaglandins (PGs). OSC-2 cells expressed COX-2 but not COX-1, whereas OSC-1 cells expressed high levels of COX-1 but showed only a very weak COX-2 expression. Accordingly, PGE2 synthesis was 600 times higher in the OSC-2 cells as compared with the OSC-1 cells. Treatment of OSC-2 cells with the selective COX-2 inhibitors flosulide and NS-398 concentration dependently suppressed PGE2 synthesis and proliferation and also induced apoptosis. In contrast, no effect of the COX-2 inhibitors was seen in OSC-1 cells. Our data demonstrate that COX-2 is expressed in the majority of esophageal SCCs and ADCs and that COX-2-derived PGs play an important role in the regulation of proliferation and apoptosis of esophageal tumor cells. It is concluded that inhibition of COX-2 may be useful in the therapy of esophageal cancer.
基于非甾体抗炎药可降低食管癌风险这一流行病学观察结果，我们研究了环氧化酶-2（COX-2）在食管鳞状细胞癌（SCC；n = 172）和食管腺癌（ADC；n = 27）中的表达情况。通过免疫组织化学方法，我们观察到91%的SCC和78%的ADC中有COX-2表达。蛋白质印迹分析显示，与正常食管鳞状上皮相比，某些肿瘤中COX-2蛋白表达增强，而在正常组织和癌组织中COX-1蛋白的含量相似。我们还在两种食管癌细胞系（OSC-1和OSC-2）中研究了COX表达，以评估COX-2衍生前列腺素（PG）的功能相关性。OSC-2细胞表达COX-2但不表达COX-1，而OSC-1细胞表达高水平的COX-1但仅显示非常弱的COX-2表达。因此，与OSC-1细胞相比，OSC-2细胞中PGE2的合成高出600倍。用选择性COX-2抑制剂氟舒利和NS-398处理OSC-2细胞，可浓度依赖性地抑制PGE2合成和增殖，并诱导细胞凋亡。相比之下，在OSC-1细胞中未观察到COX-2抑制剂的作用。我们的数据表明，COX-2在大多数食管SCC和ADC中均有表达，且COX-2衍生的PG在食管肿瘤细胞增殖和凋亡的调节中起重要作用。结论是，抑制COX-2可能对食管癌治疗有用。
