Feng Cheng, Luo Yumei, Nian Yuanyuan, Liu Dong, Yin Xiaoran, Wu Jing, Di Jia, Zhang Rong, Zhang Jun
Division of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710003, China.
Division of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
Inflammation. 2017 Jun;40(3):818-831. doi: 10.1007/s10753-017-0526-4.
Barrett's esophagus (BE) is generally accepted as the only precursor to esophageal adenocarcinoma (EAC). Deoxycholic acid (DCA)-induced inflammation and apoptotic resistance play an important role in the carcinogenesis and progression from BE to EAC. Diallyl disulfide (DADS) is a garlic-derived natural organosulfur compound. This study investigated whether DADS has chemopreventive effects against BE and the potentially related signaling pathway. BAR-T cells were treated with DCA in the presence or absence of DADS. An MTT assay was used to detect the viability of the cells. The apoptosis rate of the cells was measured by light microscopy and flow cytometry. ROS levels were determined by fluorescence microscopy and flow cytometry. Real-time PCR and ELISA were used to detect mRNA and protein levels, respectively. The levels of target proteins were also determined by western blot analysis. DADS did not inhibit cell viability in a certain concentration range. DADS, similar to the NF-κB inhibitor PDTC, inhibited the DCA-induced ROS production, inflammatory factors, IκBα phosphorylation, and expression of p50 in the nucleus in a dose-dependent manner. DADS also increased the cell apoptosis rate through down-regulating the level of Bcl-2. DADS has low cytotoxicity in BAR-T cells. It has an anti-inflammatory effect in BAR-T cells through inhibiting ROS and the NF-κB signaling pathway. Further, it abolishes the apoptotic resistance induced by DCA in an NF-κB/Bcl-2 dependent manner. DADS may be a good candidate for BE and EAC chemical prevention and therapy.
巴雷特食管(BE)通常被认为是食管腺癌(EAC)的唯一前驱病变。脱氧胆酸(DCA)诱导的炎症和凋亡抵抗在从BE到EAC的癌变和进展过程中起重要作用。二烯丙基二硫醚(DADS)是一种源自大蒜的天然有机硫化合物。本研究调查了DADS是否对BE具有化学预防作用以及潜在的相关信号通路。在有或没有DADS存在的情况下,用DCA处理BAR-T细胞。采用MTT法检测细胞活力。通过光学显微镜和流式细胞术测量细胞凋亡率。通过荧光显微镜和流式细胞术测定活性氧(ROS)水平。分别使用实时定量聚合酶链反应(Real-time PCR)和酶联免疫吸附测定(ELISA)检测mRNA和蛋白质水平。还通过蛋白质免疫印迹分析确定靶蛋白水平。在一定浓度范围内,DADS不抑制细胞活力。与核因子κB(NF-κB)抑制剂吡咯烷二硫代氨基甲酸酯(PDTC)类似,DADS以剂量依赖的方式抑制DCA诱导的ROS产生、炎性因子、IκBα磷酸化以及细胞核中p50的表达。DADS还通过下调Bcl-2水平增加细胞凋亡率。DADS在BAR-T细胞中具有低细胞毒性。它通过抑制ROS和NF-κB信号通路在BAR-T细胞中发挥抗炎作用。此外,它以NF-κB/ Bcl-2依赖的方式消除DCA诱导的凋亡抵抗。DADS可能是BE和EAC化学预防和治疗的良好候选物。