Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
Prostaglandins Other Lipid Mediat. 2011 Nov;96(1-4):27-36. doi: 10.1016/j.prostaglandins.2011.08.004. Epub 2011 Aug 16.
Inflammation in the tumor microenvironment is now recognized as one of the hallmarks of cancer. Endogenously produced lipid autacoids, locally acting small molecule lipid mediators, play a central role in inflammation and tissue homeostasis, and have recently been implicated in cancer. A well-studied group of autacoid mediators that are the products of arachidonic acid metabolism include: the prostaglandins, leukotrienes, lipoxins and cytochrome P450 (CYP) derived bioactive products. These lipid mediators are collectively referred to as eicosanoids and are generated by distinct enzymatic systems initiated by cyclooxygenases (COX 1 and 2), lipoxygenases (5-LOX, 12-LOX, 15-LOXa, 15-LOXb), and cytochrome P450s, respectively. These pathways are the target of approved drugs for the treatment of inflammation, pain, asthma, allergies, and cardiovascular disorders. Beyond their potent anti-inflammatory and anti-cancer effects, non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 specific inhibitors have been evaluated in both preclinical tumor models and clinical trials. Eicosanoid biosynthesis and actions can also be directly influenced by nutrients in the diet, as evidenced by the emerging role of omega-3 fatty acids in cancer prevention and treatment. Most research dedicated to using eicosanoids to inhibit tumor-associated inflammation has focused on the COX and LOX pathways. Novel experimental approaches that demonstrate the anti-tumor effects of inhibiting cancer-associated inflammation currently include: eicosanoid receptor antagonism, overexpression of eicosanoid metabolizing enzymes, and the use of endogenous anti-inflammatory lipid mediators. Here we review the actions of eicosanoids on inflammation in the context of tumorigenesis. Eicosanoids may represent a missing link between inflammation and cancer and thus could serve as therapeutic target(s) for inhibiting tumor growth.
肿瘤微环境中的炎症现在被认为是癌症的特征之一。内源性产生的脂质自体活性物质，即局部作用的小分子脂质介质，在炎症和组织动态平衡中发挥核心作用，并且最近与癌症有关。一组研究充分的自体活性物质介质是花生四烯酸代谢的产物，包括：前列腺素、白三烯、脂氧素和细胞色素 P450（CYP）衍生的生物活性产物。这些脂质介质统称为类二十烷酸，由环加氧酶（COX1 和 COX2）、脂加氧酶（5-LOX、12-LOX、15-LOXa、15-LOXb）和细胞色素 P450 分别启动的不同酶系统生成。这些途径是治疗炎症、疼痛、哮喘、过敏和心血管疾病的批准药物的靶点。除了具有强大的抗炎和抗癌作用外，非甾体抗炎药（NSAIDs）和 COX-2 特异性抑制剂已在临床前肿瘤模型和临床试验中进行了评估。膳食中的营养素也可以直接影响类二十烷酸的生物合成和作用，这一点可以从ω-3 脂肪酸在癌症预防和治疗中的新兴作用得到证明。大多数致力于使用类二十烷酸抑制与肿瘤相关的炎症的研究都集中在 COX 和 LOX 途径上。目前，证明抑制与癌症相关的炎症的抗肿瘤作用的新实验方法包括：类二十烷酸受体拮抗作用、类二十烷酸代谢酶的过表达以及内源性抗炎脂质介质的使用。在这里，我们综述了类二十烷酸在肿瘤发生过程中对炎症的作用。类二十烷酸可能是炎症和癌症之间缺失的一环，因此可以作为抑制肿瘤生长的治疗靶点。
