Cha Yong I, DuBois Raymond N
Department of Medicine, Cell and Developmental Biology and Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6838, USA.
Annu Rev Med. 2007;58:239-52. doi: 10.1146/annurev.med.57.121304.131253.
Preclinical and clinical studies have clearly shown a benefit of nonsteroidal anti-inflammatory drug (NSAID) use in reducing cancer risk. However, the adverse gastrointestinal and cardiovascular side effects associated with NSAIDs and COX-2 selective inhibitors (coxibs) have provoked more scrutiny of the precise role of specific downstream mediators in the prostaglandin (PG) signaling cascade. NSAIDs and coxibs inhibit PG biosynthesis. One of the PGs produced at high levels in the tumor microenvironment is PGE(2), which is thought to play a major role in cancer progression. Thus, a better understanding of PGE(2) signaling could enable identification of novel and safer therapeutic targets downstream of the cyclooxygenase enzymes. We review the emerging molecular mechanisms by which COX-2-derived PGE(2) is involved in cancer progression and delineate potential opportunities for development of novel pharmacologic approaches utilizing this pathway.
临床前和临床研究已明确显示，使用非甾体抗炎药（NSAID）对降低癌症风险有益。然而，与NSAIDs和COX-2选择性抑制剂（coxibs）相关的不良胃肠道和心血管副作用，引发了对前列腺素（PG）信号级联中特定下游介质确切作用的更多审视。NSAIDs和coxibs抑制PG生物合成。肿瘤微环境中高水平产生的PG之一是PGE(2)，其被认为在癌症进展中起主要作用。因此，更好地理解PGE(2)信号传导，可能有助于识别环氧化酶下游新的、更安全的治疗靶点。我们综述了COX-2衍生的PGE(2)参与癌症进展的新出现的分子机制，并阐述了利用该途径开发新型药理学方法的潜在机会。
