Jiang Qianqian, Fan Guoxia, Wu Kaiwei
Traditional Chinese Medicine Department, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, 257091, China.
Cell Biochem Biophys. 2025 Mar;83(1):1035-1044. doi: 10.1007/s12013-024-01536-x. Epub 2024 Sep 19.
Chronic atrophic gastritis (CAG) is a critical initial step in gastric cancer tumorigenesis accompanied by high malignancy. Erianin has been proposed as a promising agent in treating precancerous lesions of gastric cancer. Considering that little work has been implemented concerning the specific role and possible regulatory mechanism of Erianin in CAG, the goal of the study is to disclose the effects and mechanism of erianin on the malignant transformation in the process of CAG. CAG cell model was generated in human gastric epithelium GES-1 cells induced by Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG). CCK-8 method determined cell viability. ELISA and corresponding assay kits severally appraised the contents of inflammatory cytokines and oxidative stress markers. Cellular reactive oxygen species (ROS) formation was measured by flow cytometry analysis using DCFH-DA probe. GFP-LC3 immunofluorescence staining and Western blotting evaluated autophagy. Also, Western blotting analyzed the expression of components in mitogen activated protein kinase (MAPK)/mechanistic target of rapamycin (mTOR) signaling. The results manifested that MNNG treatment diminished the viability and autophagy whereas intensified the inflammation and oxidative stress in GES-1 cells, which were all reversed by Erianin. Besides, Erianin blocked mTOR/MAPK signaling in MNNG-exposed GES-1 cells. Autophagy inhibitor 3-methyladenine (3-MA) or p38 MAPK agonist asiatic acid partially counteracted the protection elicited by Erianin against viability loss, inflammatory reaction as well as oxidative stress in MNNG-induced GES-1 cells. Combined with the findings, Erianin might mediate autophagy to improve MNNG-elicited CAG via MAPK/mTOR signaling.
慢性萎缩性胃炎（CAG）是胃癌发生的关键起始步骤，具有高度恶性。毛兰素已被认为是治疗胃癌癌前病变的一种有前景的药物。鉴于关于毛兰素在CAG中的具体作用和可能的调控机制的研究较少，本研究的目的是揭示毛兰素对CAG过程中恶性转化的影响及机制。通过N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱导人胃上皮GES-1细胞建立CAG细胞模型。采用CCK-8法检测细胞活力。ELISA和相应的检测试剂盒分别评估炎症细胞因子和氧化应激标志物的含量。使用DCFH-DA探针通过流式细胞术分析测定细胞活性氧（ROS）的形成。通过绿色荧光蛋白-微管相关蛋白1轻链3（GFP-LC3）免疫荧光染色和蛋白质免疫印迹法评估自噬。此外，蛋白质免疫印迹法分析丝裂原活化蛋白激酶（MAPK）/雷帕霉素靶蛋白（mTOR）信号通路中各组分的表达。结果表明，MNNG处理降低了GES-1细胞的活力和自噬，同时增强了炎症和氧化应激，而毛兰素可逆转这些作用。此外，毛兰素阻断了MNNG处理的GES-1细胞中的mTOR/MAPK信号通路。自噬抑制剂3-甲基腺嘌呤（3-MA）或p38 MAPK激动剂齐墩果酸部分抵消了毛兰素对MNNG诱导的GES-1细胞活力丧失、炎症反应和氧化应激的保护作用。综合这些结果，毛兰素可能通过MAPK/mTOR信号通路介导自噬来改善MNNG诱导的CAG。
