Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Int J Mol Sci. 2021 Dec 23;23(1):120. doi: 10.3390/ijms23010120.
Cancer remains a leading cause of death worldwide, despite many advances being made in recent decades. Changes in the tumor microenvironment, including dysregulated immunity, may contribute to carcinogenesis and cancer progression. The cysteinyl leukotriene (CysLT) pathway is involved in several signal pathways, having various functions in different tissues. We summarized major findings of studies about the roles of the CysLT pathway in cancer. Many in vitro studies suggested the roles of CysLTs in cell survival/proliferation via CysLT receptor (CysLTR). CysLTR antagonism decreased cell vitality and induced cell death in several types of cancer cells, such as colorectal, urological, breast, lung and neurological malignancies. CysLTs were also associated with multidrug resistance of cancer, and CysLTR antagonism might reverse chemoresistance. Some animal studies demonstrated the beneficial effects of CysLTR antagonist in inhibiting tumorigenesis and progression of some cancer types, particularly colorectal cancer and lung cancer. The expression of CysLTR was shown in various cancer tissues, particularly colorectal cancer and urological malignancies, and higher expression was associated with a poorer prognosis. The chemo-preventive effects of CysLTR antagonists were demonstrated in two large retrospective cohort studies. In summary, the roles of the CysLT pathway in cancer have been delineated, whereas further studies are still warranted.
尽管近年来在医学领域取得了许多进展，但癌症仍然是全球主要的死亡原因。肿瘤微环境的变化，包括失调的免疫，可能导致癌症的发生和发展。半胱氨酰白三烯（CysLT）途径参与了几个信号通路，在不同的组织中具有不同的功能。我们总结了关于 CysLT 途径在癌症中的作用的主要研究结果。许多体外研究表明 CysLT 通过 CysLT 受体（CysLTR）在细胞存活/增殖中发挥作用。CysLTR 拮抗剂降低了几种类型的癌细胞（如结直肠、泌尿系统、乳腺、肺和神经恶性肿瘤）的细胞活力并诱导其死亡。CysLT 还与癌症的多药耐药性有关，CysLTR 拮抗剂可能逆转化疗耐药性。一些动物研究表明 CysLTR 拮抗剂在抑制某些癌症类型（特别是结直肠癌和肺癌）的肿瘤发生和进展方面具有有益作用。CysLTR 在各种癌症组织中表达，特别是在结直肠和泌尿系统恶性肿瘤中，其高表达与预后不良相关。两项大型回顾性队列研究表明了 CysLTR 拮抗剂的化学预防作用。总之，CysLT 途径在癌症中的作用已经被描绘出来，但仍需要进一步的研究。
