Department of Gastroenterology, The Second Affiliated Hospital of School of Medicine, Xi'an Jiaotong University, No. 157, Xi Wu Road, Xi'an, 710004, Shaanxi Province, China.
Dig Dis Sci. 2014 Jan;59(1):89-97. doi: 10.1007/s10620-013-2877-5. Epub 2013 Oct 5.
Deoxycholic acid (DCA) promotes the development and progression of esophageal adenocarcinoma (EAC) by inducing inflammation. Adiponectin is reported to have anti-inflammatory and anti-tumor effects.
This study investigated the effects of two types of adiponectin, full-length adiponectin (f-Ad) and globular adiponectin (g-Ad), on DCA-induced inflammation, and investigated the involvement of the reactive oxygen species (ROS)/NF-κB signaling pathway in inflammation in EAC.
OE19 cells were treated with DCA (50-300 μM) and/or f-Ad/g-Ad (10.0 μg/ml) or N-acetylcysteine (NAC). The viability of cells exposed to DCA was measured by use of the MTT assay. mRNA and protein levels of the inflammatory factors were examined by real-time PCR and ELISA. Intra-cellular ROS levels were determined by use of flow cytometry. Protein levels of total and p-NF-κB p65 were measured by western blot.
DCA induced dose and time-dependent cytotoxicity. mRNA and protein expression of TNF-α, IL-8, and IL-6 in cells treated with DCA alone were up-regulated, and intra-cellular ROS and p-NF-κB p65 protein levels were also increased. g-Ad promoted inflammatory factor production, ROS levels, and p-NF-κB p65 protein expression whereas f-Ad had a suppressive effect. When combined with DCA, g-Ad enhanced the pro-inflammatory effect of DCA whereas f-Ad, similar to NAC, suppressed the effect.
DCA has a pro-inflammatory effect in EAC. f-Ad has an anti-inflammatory effect whereas g-Ad seems to have a pro-inflammatory effect in an ROS/NF-κB p65-dependent manner. This indicates that f-Ad could be a potential anti-inflammatory reagent for cancer therapy.
脱氧胆酸（DCA）通过诱导炎症促进食管腺癌（EAC）的发展和进展。脂联素具有抗炎和抗肿瘤作用。
本研究探讨了两种类型的脂联素，全长脂联素（f-Ad）和球状脂联素（g-Ad）对 DCA 诱导的炎症的影响，并研究了活性氧（ROS）/NF-κB 信号通路在 EAC 炎症中的作用。
OE19 细胞用 DCA（50-300 μM）和/或 f-Ad/g-Ad（10.0 μg/ml）或 N-乙酰半胱氨酸（NAC）处理。用 MTT 法测定暴露于 DCA 的细胞活力。通过实时 PCR 和 ELISA 检测炎症因子的 mRNA 和蛋白水平。通过流式细胞术测定细胞内 ROS 水平。通过 Western blot 测定总 NF-κB p65 和 p-NF-κB p65 蛋白水平。
DCA 诱导剂量和时间依赖性细胞毒性。单独用 DCA 处理的细胞中 TNF-α、IL-8 和 IL-6 的 mRNA 和蛋白表达上调，细胞内 ROS 和 p-NF-κB p65 蛋白水平也升高。g-Ad 促进炎症因子产生、ROS 水平和 p-NF-κB p65 蛋白表达，而 f-Ad 则具有抑制作用。当与 DCA 联合使用时，g-Ad 增强了 DCA 的促炎作用，而 f-Ad 则与 NAC 相似，抑制了该作用。
DCA 在 EAC 中具有促炎作用。f-Ad 具有抗炎作用，而 g-Ad 似乎以 ROS/NF-κB p65 依赖的方式具有促炎作用。这表明 f-Ad 可能是癌症治疗的潜在抗炎试剂。
