Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
Sickle Cell Institute Chhattisgarh, Raipur, Chhattisgarh, 492001, India.
Crit Rev Oncol Hematol. 2018 Jul;127:50-55. doi: 10.1016/j.critrevonc.2018.05.012. Epub 2018 May 18.
Lipoxygenases (LOXs) are dioxygenases that catalyze the peroxidation of linoleic acid (LA) or arachidonic acid (AA), in the presence of molecular oxygen. The existence of inflammatory component in the tumor microenvironment intimately links the LOXs to gastrointestinal (GI) cancer progression. Amongst the six-different human LOX-isoforms, 5-LOX is the most vital enzyme for leukotriene (LT) biosynthesis, which is the main inflammation intermediaries. As recent investigations have shown the association of 5-LOX with tumor metastasis, there has also been significant progress in discovering the function of 5-LOX pathway in GI cancer. Studies on GI cancer cells using the pharmacological drugs targeting 5-LOX pathway have shown antiproliferative and proapoptotic effects. Pharmacogenetic discoveries in other diseases have revealed strong heritable basis for the leukotriene pathway, which helps in exploring the mechanistic source of genetic alteration within the leukotriene pathway and offer insights into GI cancer pathogenesis and future prospects for treatment and prevention. This review recapitulates the current research status of 5-LOX activity in GI malignancies.
脂氧合酶（LOXs）是一类双加氧酶，能够在分子氧存在的条件下催化亚油酸（LA）或花生四烯酸（AA）的过氧化反应。肿瘤微环境中的炎症成分与胃肠道（GI）癌症的进展密切相关，LOXs 也与之密切相关。在六种不同的人类 LOX 同工酶中，5-LOX 是白三烯（LT）生物合成的最重要的酶，是主要的炎症介质。最近的研究表明 5-LOX 与肿瘤转移有关，因此在 GI 癌症中发现 5-LOX 途径的功能也取得了重大进展。使用针对 5-LOX 途径的药理学药物对 GI 癌细胞进行的研究表明，其具有抗增殖和促凋亡作用。其他疾病的药物遗传学发现揭示了白三烯途径具有很强的遗传性基础，这有助于探索白三烯途径内遗传改变的机制来源，并为 GI 癌症的发病机制和未来的治疗和预防提供了新的见解。本文综述了目前 5-LOX 在胃肠道恶性肿瘤中的活性研究现状。
