Chuffa Luiz Gustavo de Almeida, Reiter Russel J, Lupi Luiz Antonio
Department of Anatomy, Institute of Biosciences, UNESP - Universidade Estadual Paulista, Botucatu-SP, Brazil and Department of Cellular and Structural Biology, UTHSCSA, San Antonio, TX 78229, USA.
Carcinogenesis. 2017 Oct 1;38(10):945-952. doi: 10.1093/carcin/bgx054.
Ovarian cancer (OC) has the highest mortality rate of all gynecological cancers, and most patients develop chemoresistance after first-line treatments. Despite recent advances, the 5-year relative survival is ~45% for all OC subtypes, and invasive epithelial OC has only a 17% survival rate when diagnosed at a late stage. Identification of new efficacious molecules or biomarkers represents important opportunities in the treatment of OC. The pharmacological and physiological properties of melatonin indicate this agent could be useful against OC progression and metastasis. In normal cells, melatonin has potent antioxidant and anti-apoptotic actions. Conversely, melatonin has pro-oxidant as well as anti-proliferative, anti-angiogenic and immunomodulatory properties in many cancer types including hormone-dependent cancers. Although melatonin receptors have been identified in OC cells, the exact mechanism by which melatonin induces anticancer activities remains incompletely understood. Clinical studies have reported negative correlation between aggressiveness of OC and serum levels of melatonin, reinforcing the idea that melatonin may be a critical factor determining OC development. In vitro and in vivo studies suggest melatonin differentially regulates multiple signaling pathways in OC cells. This focused review explores the potential mechanisms of action of melatonin on cultured OC cells and in experimental models of OC in an attempt to clarify how melatonin modulates the signaling pathways involved in cancer cell apoptosis, survival, inflammation, proliferation and metabolic processes. Based on the evidence presented, we feel that melatonin, as an agent that controls cellular signals associated with malignancy, may be beneficial in combination with other therapeutics for OC treatment.
卵巢癌（OC）在所有妇科癌症中死亡率最高，大多数患者在一线治疗后会产生化疗耐药性。尽管近年来取得了进展，但所有OC亚型的5年相对生存率约为45%，侵袭性上皮性OC在晚期诊断时的生存率仅为17%。鉴定新的有效分子或生物标志物是OC治疗中的重要机遇。褪黑素的药理和生理特性表明该药物可能对OC的进展和转移有用。在正常细胞中，褪黑素具有强大的抗氧化和抗凋亡作用。相反，在包括激素依赖性癌症在内的许多癌症类型中，褪黑素具有促氧化以及抗增殖、抗血管生成和免疫调节特性。尽管在OC细胞中已鉴定出褪黑素受体，但褪黑素诱导抗癌活性的确切机制仍未完全了解。临床研究报告了OC的侵袭性与血清褪黑素水平之间的负相关，强化了褪黑素可能是决定OC发展的关键因素这一观点。体外和体内研究表明，褪黑素可差异调节OC细胞中的多种信号通路。这篇重点综述探讨了褪黑素对培养的OC细胞和OC实验模型的潜在作用机制，试图阐明褪黑素如何调节参与癌细胞凋亡、存活、炎症、增殖和代谢过程的信号通路。基于所提供的证据，我们认为褪黑素作为一种控制与恶性肿瘤相关的细胞信号的药物，可能与其他疗法联合用于OC治疗有益。
