Department of Psychological & Brain Sciences, University of Iowa, United States.
Department of Psychology, University of Miami, United States.
Psychoneuroendocrinology. 2019 Aug;106:244-251. doi: 10.1016/j.psyneuen.2019.04.007. Epub 2019 Apr 6.
Prior research demonstrates a protective role for oxytocin in ovarian cancer based on its anti-proliferative, anti-migratory, and anti-invasive effects in vitro and in vivo. However, the role of endogenous oxytocin has not been examined in ovarian cancer patients. Oxytocin also has anti-inflammatory properties that have not been examined in cancer. The purpose of this investigation was to examine relationships between endogenous oxytocin, tumor-associated inflammation (interleukin-6), and survival in advanced epithelial ovarian cancer patients.
Tumor microenvironment (ascites) and plasma oxytocin levels were analyzed via ELISA on extracted samples obtained from 79 patients. In vitro models were used to characterize oxytocin and oxytocin receptor expression in four ovarian cancer cell lines and to investigate direct anti-inflammatory effects of oxytocin on tumor cell secretion of interleukin-6. High and variable levels of oxytocin were observed in ascites, up to 200 times greater than in plasma. Higher levels of ascites oxytocin were associated with lower levels of systemic and tumor-associated interleukin-6, an inflammatory cytokine implicated in ovarian tumor progression. Oxytocin also attenuated interleukin-6 secretion from multiple ovarian tumor cell lines in vitro. Higher levels of ascites oxytocin were associated with a significant survival advantage and statistical mediation analyses suggested this effect was partially mediated by interleukin-6.
These data identify a previously unacknowledged hormone in the ovarian tumor microenvironment and provide initial evidence that oxytocin has protective effects in ovarian cancer via anti-inflammatory mechanisms. Future studies should examine the therapeutic utility of oxytocin.
先前的研究表明，催产素在卵巢癌中具有保护作用，这是基于其在体外和体内的抗增殖、抗迁移和抗侵袭作用。然而，尚未在卵巢癌患者中检查内源性催产素的作用。催产素还具有抗炎特性，尚未在癌症中进行过研究。本研究旨在检查内源性催产素、肿瘤相关炎症（白细胞介素-6）与晚期上皮性卵巢癌患者生存之间的关系。
通过 ELISA 分析从 79 名患者中提取样本的肿瘤微环境（腹水）和血浆催产素水平。使用体外模型来表征四种卵巢癌细胞系中的催产素和催产素受体表达，并研究催产素对肿瘤细胞白细胞介素-6分泌的直接抗炎作用。在腹水中观察到高且可变的催产素水平，高达血浆的 200 倍以上。较高的腹水催产素水平与较低的系统性和肿瘤相关白细胞介素-6水平相关，白细胞介素-6是一种与卵巢肿瘤进展有关的炎症细胞因子。催产素还可减弱多种卵巢肿瘤细胞系在体外的白细胞介素-6分泌。较高的腹水催产素水平与显著的生存优势相关，统计中介分析表明，这种作用部分是通过白细胞介素-6介导的。
这些数据确定了卵巢肿瘤微环境中以前未被承认的激素，并提供了初步证据，表明催产素通过抗炎机制对卵巢癌具有保护作用。未来的研究应检查催产素的治疗效用。
