Grösch Sabine, Maier Thorsten Jürgen, Schiffmann Susanne, Geisslinger Gerd
Pharmazentrum Frankfurt, ZAFES, Institut für klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe, Universität Frankfurt, Theodor Stern Kai 7, Frankfurt/Main, Germany.
J Natl Cancer Inst. 2006 Jun 7;98(11):736-47. doi: 10.1093/jnci/djj206.
Nonsteroidal antiinflammatory drugs (NSAIDs) appear to reduce the risk of developing cancer. One mechanism through which NSAIDs act to reduce carcinogenesis is to inhibit the activity of cyclooxygenase-2 (COX-2), an enzyme that is overexpressed in various cancer tissues. Overexpression of COX-2 increases cell proliferation and inhibits apoptosis. However, selective COX-2 inhibitors can also act through COX-independent mechanisms. In this review, we describe the COX-2-independent molecular targets of these COX-2 inhibitors and discuss how these targets may be involved in the anticarcinogenic activities of these selective COX-2 inhibitors. We also compare the concentrations of these inhibitors used in in vitro and in vivo experiments and discuss the implications of the in vitro studies for clinical management of cancer with these drugs.
非甾体抗炎药（NSAIDs）似乎能降低患癌风险。NSAIDs发挥抗癌作用的一种机制是抑制环氧合酶-2（COX-2）的活性，该酶在多种癌症组织中过度表达。COX-2的过度表达会增加细胞增殖并抑制细胞凋亡。然而，选择性COX-2抑制剂也可通过不依赖COX的机制发挥作用。在本综述中，我们描述了这些COX-2抑制剂不依赖COX的分子靶点，并讨论了这些靶点可能如何参与这些选择性COX-2抑制剂的抗癌活性。我们还比较了体外和体内实验中使用的这些抑制剂的浓度，并讨论了体外研究对这些药物在癌症临床治疗中的意义。
