Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential
Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential
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DOI：
10.1073/pnas.94.7.3336
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发表时间：
1997-04-01
影响因子：
11.1
通讯作者：
DuBois, RN
中科院分区：
文献类型：
--
作者：
Tsujii, M;Kawano, S;DuBois, RN
最近的流行病学研究表明，与不服用这些药物的人相比，定期服用非甾体类药物的人结直肠癌死亡率降低40 - 50%。所有这些药物的一个共同特性是它们能够抑制环加氧酶（COY），这是一种将花生四烯酸转化为花生四烯酸的小桶酶。COX-2在人和啮齿类动物的肠肿瘤中高水平表达。用COX-2表达载体或缺少COX-2插入片段的相同载体永久转染人结肠癌细胞（Caco-2），组成型表达COX-2的Caco-2细胞，与亲本Caco-2细胞或载体转染的对照细胞相比，获得了增加的侵袭力。与这种表型变化相关的生化变化包括金属蛋白酶-2的活化和膜型金属蛋白酶的RNA水平的增加，侵袭性的增加和前列腺素的产生通过用舒林酸硫化物（一种已知的考克斯抑制剂）治疗而逆转。这些研究表明，组成型表达考克斯-2可导致改变结肠直肠癌细胞的转移潜能的表型变化。
Recent epidemiologic studies have shown a 40-50% reduction in mortality from colorectal cancer in individuals who take nonsteroidal antiinflammatory drugs on a regular basis compared with those not taking these agents, One property shared bg all of these drugs is their ability to inhibit cyclooxygenase (COY), a keg enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of COX have been characterized, COX-I and COX-2, COX-2 is expressed at high levels in intestinal tumors in humans and rodents, Human colon cancer tells (Caco-2) were permanently transfected with a COX-2 expression vector or the identical vector lacking the COX-2 insert, The Caco-2 cells, which constitutively expressed COX-2, acquired increased invasiveness compared with the parental Caco-2 cells or the vector transfected control cells. Biochemical changes associated with this phenotypic change included activation of metalloproteinase-2 and increased RNA levels for the membrane-type metalloproteinase, increased invasiveness and prostaglandin production were reversed by treatment with sulindac sulfide, a known COX inhibitor, These studies demonstrate that constitutive expression of COX-2 can lead to phenotypic changes that alter the metastatic potential of colorectal cancer cells.