Expression of cyclooxygenase-1 and -2 in human colorectal cancer.
Expression of cyclooxygenase-1 and -2 in human colorectal cancer.
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发表时间：
1995-09
期刊：
影响因子：
11.2
通讯作者：
H. Sano;Y. Kawahito;R. Wilder;A. Hashiramoto;S. Mukai;K. Asai;S. Kimura;H. Kato;M. Kondo;T. Hla
中科院分区：
文献类型：
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作者：
H. Sano;Y. Kawahito;R. Wilder;A. Hashiramoto;S. Mukai;K. Asai;S. Kimura;H. Kato;M. Kondo;T. Hla
一些研究表明，非甾体抗炎药，包括吲哚美辛，阿司匹林，舒林酸和吡罗昔康降低结肠癌的风险。此外，抑制环氧化酶（考克斯）酶的非甾体抗炎药在致癌动物模型中显示出抑制结肠癌的发展。非甾体抗炎药抑制考克斯酶的组成型（考克斯-1）和诱导型（考克斯-2）同种型的酶活性。我们用免疫组织化学方法研究了考克斯-1和考克斯-2多肽在人结肠癌组织中的表达。15例临床诊断为结直肠癌的结肠癌组织中观察到考克斯-2表达增强。考克斯-2在病变组织的癌细胞、炎性细胞、血管内皮细胞和成纤维细胞中的表达明显高于正常结肠组织和非病变结肠组织。考克斯-2在癌细胞中的表达范围和强度均明显大于其它类型的细胞。相反，考克斯-1多肽在正常和癌组织中的表达较弱。这些数据表明，结肠癌组织中考克斯-2基因的表达增强可能有助于结肠癌组织中前列腺素E2的合成增强。考克斯-2的高表达可能在结肠癌的发病机制中起一定作用。此外，选择性抑制考克斯-2可能被证明在延缓结肠癌发展方面更有效。
Several studies indicate that nonsteroidal anti-inflammatory drugs including indomethacin, aspirin, sulindac, and piroxicam reduce the risk of colon cancer. Furthermore, nonsteroidal anti-inflammatory drugs that inhibit the cyclooxygenase (COX) enzyme were shown to inhibit the development of colon cancer in animal models of carcinogenesis. Non-steroidal anti-inflammatory drugs inhibit the enzymatic activity of both the constitutive (COX-1) and inducible (COX-2) isoforms of COX enzyme. We have investigated the expression of COX-1 and COX-2 polypeptides in human colon cancer tissues using immunohistochemistry. Enhanced COX-2 expression was observed in colon cancer tissues from 15 subjects with clinically diagnosed colorectal cancer. Marked COX-2 expression was observed in cancer cells, inflammatory cells, vascular endothelium, and fibroblasts of the lesional tissues compared with the nonlesional and normal colon tissues. The extent and intensity of the immunoreactive COX-2 in cancer cells was much greater than that of the other cell types. In contrast, the expression of COX-1 polypeptide was weak in both normal and cancerous specimens. These data suggest that the enhanced expression of the COX-2 gene in colon cancer tissues may contribute to the enhanced synthesis of prostaglandin E2 by the colon cancer tissues. Enhanced expression of COX-2 may play a role in the pathogenesis of colon cancer. Furthermore, selective inhibition of COX-2 may prove to be more efficacious in the retardation of colon cancer development.