Cyclooxygenases in hepatocellular carcinoma  

作　　者：Melchiorre Cervello Giuseppe Montalto 

机构地区：[1]Institute of Biomedicine and Molecular Immunology "Alberto Monroy" National Research Council,Palermo,Italy [2]Department of Clinical Medicine University of Palermo,Palermo,Italy

出　　处：《World Journal of Gastroenterology》2006年第32期5113-5121,共9页世界胃肠病学杂志（英文版）

基　　金：Supported by a grant from the Associazione Italiana per la Ricerca sul Cancro and from the Italian Ministero dell'Universitàedella Ricerca Scientifica (ex 60%, year 2003)

摘　　要：Many epidemiological studies demonstrate that treatment with non-steroidal anti-inflammatory drugs （NSAIDs） reduce the incidence and mortality of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase （COX） enzymes are well-known targets of NSAIDs. However, conventional NSAIDs nonselectively inhibit both the constitutive form COX-1, and the inducible form COX-2. Recent evidence indicates that COX-2 is an important molecular target for anticancer therapies. Its expression is undetectable in most normal tissues, and is highly induced by proinflammatory cytokines, mitogens, tumor promoters and growth factors. It is now well-established that COX-2 is chronically overexpressed in many premalignant, malignant, and metastastic cancers, including hepatocellular carcinoma （HCC）. Overexpression of COX-2 in patients with HCC is generally higher in welldifferentiated HCCs compared with less-differentiated HCCs or histologically normal liver, suggesting that COX-2 may be involved in the early stages of hepatocarcinogenesis, and increased expression of COX-2 in noncancerous liver tissue has been significantly associated with shorter disease-free survival in patients with HCC. In tumors, overexpression of COX-2 leads to an increase in prostaglandin （PG） levels, which affect many mechanisms involved in carcinogenesis, such as angiogenesis, inhibition of apoptosis, stimulation of cell growth as well as the invasiveness and metastatic potential of tumor cells. The availability of novel agents that selectively inhibit COX-2 （COXIB）, has contributed to shedding light on the role of this molecule. Experimental studies on animal models of liver cancer have shown that NSAIDs, including both selective and non-selective COX-2 inhibitors, exert chemopreventive as well as therapeutic effects. However, the key mechanism by which COX-2 inhibitors affect HCC cell growth is as yet not fully understood. Increasing evidence suggests the involvement of molecular targets other than COX-2 in the antiprol许多流行病学的研究与反煽动性的药(NSAID ) 减少的 non-steroidal 表明那治疗某些恶意的发生和死亡，特别胃肠的癌症。cyclooxygenase (艇长) 酶是 NSAID 的著名目标。然而，常规 NSAID 非有选择地禁止组成的形式 COX-1，和可诱导的形式 COX-2。最近的证据显示 COX-2 是为反癌症治疗的一个重要分子的目标。它的表示在很正常的纸巾是无法发现的，并且被支持 inflammatory cytokines， mitogens，肿瘤倡导者和生长因素高度导致。COX-2 是，现在是生长得很好的长期地在上在许多恶化前表示了，恶意，并且 metastastic 癌症，包括肝细胞癌(HCC ) 。在有 HCC 的病人的 COX-2 的 Overexpression 与区分更少的 HCC 或组织学地正常的肝相比在区分得好的 HCC 通常是更高的，建议 COX-2 可以涉及 hepatocarcinogenesis 的早阶段，并且在非癌的肝织物增加了 COX-2 的表示显著地与 HCC 在病人与更短的没有疾病的幸存被联系了。在肿瘤，在层次，它影响许多机制在致癌作用包含了的前列腺素(PG ) 在 COX-2 的表示上导致增加，例如血管生成， apoptosis 的抑制，房间生长的刺激以及侵略海角和肿瘤房间的变形潜力。有选择地禁止 COX-2 (COXIB ) 的新奇代理人的可获得性，贡献了使这个分子的角色清楚些。肝癌症的动物模型上的试验性的研究证明了包括选择、非选择的 COX-2 禁止者， NSAID 象治疗学的效果一样施加 chemopreventive。然而， COX-2 禁止者由影响 HCC 细胞生长的关键机制不充分迄今为止被理解。增加的证据在 COX-2 选择禁止者的 anti-proliferative 效果建议除 COX-2 以外的分子的目标的参与。因此，艇长禁止者可以使用 COX-2-dependent 和 COX-2-independent 机制调停他们的反肿瘤性质，尽管他们向在活体内效果的相对贡献留下，更少变清。这里，我们考察艇长酶的特征，在他们可以由贡献 HCC 生长的 hepatocarcinogen

关 键 词：CYCLOOXYGENASE-2 CYCLOOXYGENASE-1 Hepatocellular carcinoma Non-steroidal antiinflammatory drugs Inhibit cyclooxygenase-2 

分 类 号：R735.7[医药卫生—肿瘤]