Xue Jian-Jun, Zhang Ling-Yun, Hou Huai-Jing, Li Yan, Liang Wan-Sheng, Yang Ke-Hu
Evidence Based Medicine Centre, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou 730000, China.
Iran J Basic Med Sci. 2018 Dec;21(12):1297-1304. doi: 10.22038/ijbms.2018.29141.7039.
To analyze the potential influences of propofol on the oxidative stress of HO-induced human esophageal squamous cell carcinoma (ESCC) Eca109 cell through mediating the Wnt/β-catenin signaling pathway.
Eca109 cells were classified into 5 groups: Control group, HO group, Propofol + HO group, Dkk1 (Dickkopf-1, Wnt/β-catenin pathway antagonist) + HO group, and Propofol + LiCl (Lithium chloride, Wnt/β-catenin pathway agonist) + HO group. Western blotting was performed to determine the protein expressions, flow cytometry to measure the content of ROS, immunofluorescence staining to detect the oxidative DNA damage, as well as MTT, AnnexinV-FITC/PI, Wound-healing, and Transwell assays to test the biological characteristics of Eca109 cells.
HO resulted in the increased nuclear and cytoplasmatic expression of β-catenin, reduced p-GSK3β expression, up-regulated ROS content, and induced oxidative DNA damage in Eca109 cells. Moreover, Eca109 cells treated with HO alone had enhanced cell proliferation and metastasis but decreased cell apoptosis, as compared with those without any treatment; meanwhile, the declined Cyt C, Bax, and cleaved caspase-3, as well as the elevated Bcl-2 were also observed in Eca109 cells in the HO group, which were reversed by Propofol or Dkk1. Moreover, Propofol could inhibit the effect of LiCl on activating the Wnt/β-catenin signaling pathway in HO-induced Eca109 cells.
Propofol elicits protective effects to inhibit HO-induced proliferation and metastasis and promote apoptosis of Eca109 cells via blocking the Wnt/β-catenin pathway, offering a possible therapeutic modality for ESCC.
通过介导Wnt/β-连环蛋白信号通路，分析丙泊酚对过氧化氢（HO）诱导的人食管鳞状细胞癌（ESCC）Eca109细胞氧化应激的潜在影响。
将Eca109细胞分为5组：对照组、HO组、丙泊酚+HO组、Dkk1（Dickkopf-1，Wnt/β-连环蛋白通路拮抗剂）+HO组、丙泊酚+氯化锂（LiCl，Wnt/β-连环蛋白通路激动剂）+HO组。采用蛋白质印迹法检测蛋白表达，流式细胞术检测活性氧（ROS）含量，免疫荧光染色检测氧化性DNA损伤，以及采用MTT法、膜联蛋白V-异硫氰酸荧光素/碘化丙啶（AnnexinV-FITC/PI）法、划痕实验和Transwell实验检测Eca109细胞的生物学特性。
HO导致Eca109细胞中β-连环蛋白的细胞核和细胞质表达增加，p-GSK3β表达降低，ROS含量上调，并诱导氧化性DNA损伤。此外，与未处理的细胞相比，单独用HO处理的Eca109细胞增殖和转移增强，但细胞凋亡减少；同时，HO组Eca109细胞中细胞色素C（Cyt C）、Bax和裂解的半胱天冬酶-3水平下降，而Bcl-2水平升高，丙泊酚或Dkk1可逆转这些变化。此外，丙泊酚可抑制LiCl对HO诱导的Eca109细胞中Wnt/β-连环蛋白信号通路的激活作用。
丙泊酚通过阻断Wnt/β-连环蛋白通路发挥保护作用，抑制HO诱导的Eca109细胞增殖和转移并促进其凋亡，为ESCC提供了一种可能的治疗方式。
