Hung Wen-Chun
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Kaohsiung J Med Sci. 2008 Aug;24(8):392-7. doi: 10.1016/S1607-551X(08)70162-1.
Epidemiological studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the incidence and mortality of several types of human cancer. However, the molecular mechanisms by which NSAIDs exert their chemopreventive and anticancer effects are not fully understood. Cyclooxygenase 1 (COX-1) and COX-2 are the main targets for NSAIDs. Recent studies demonstrate that COX-2 is overexpressed in many human cancers and may promote tumorigenesis via: (1) stimulation of cancer cell proliferation; (2) increase of tumor angiogenesis; (3) prevention of cancer cell apoptosis; (4) modulation of immunoregulatory reactions; and (5) enhancement of tumor metastasis. NSAIDs may target the signaling molecules (from upstream activators to downstream effectors) involved in these mechanisms to attenuate the development and progression of cancer. In this review, we discuss the recent findings with regard to the mechanisms by which NSAIDs inhibit tumorigenesis and will specifically focus on the elucidation of NSAID-induced inhibition of tumor metastasis.
流行病学研究表明，非甾体抗炎药（NSAIDs）可降低几种人类癌症的发病率和死亡率。然而，NSAIDs发挥化学预防和抗癌作用的分子机制尚未完全明确。环氧化酶1（COX-1）和环氧化酶2（COX-2）是NSAIDs的主要作用靶点。最近的研究表明，COX-2在许多人类癌症中过度表达，并可能通过以下方式促进肿瘤发生：（1）刺激癌细胞增殖；（2）增加肿瘤血管生成；（3）防止癌细胞凋亡；（4）调节免疫调节反应；（5）增强肿瘤转移。NSAIDs可能靶向参与这些机制的信号分子（从上游激活剂到下游效应器），以减弱癌症的发生和发展。在本综述中，我们讨论了关于NSAIDs抑制肿瘤发生机制的最新研究结果，并将特别关注NSAIDs诱导的肿瘤转移抑制作用的阐明。
