Xing Yijuan, Lv Xiao, Chen Xi, Du Junhong, Hu Dan, He Ruifen, Liang Xiaolei, Yang Yongxiu
The First Clinical Medical College of Lanzhou University, Lanzhou 730000, Gansu, China; Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Gansu Provincial Clinical Research Center for Gynecological Oncology, Lanzhou, 730000 Gansu, China.
Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Gansu Provincial Clinical Research Center for Gynecological Oncology, Lanzhou, 730000 Gansu, China; Department of Obstetrics and Gynecology, First Hospital of Lanzhou University, Lanzhou, 730000 Gansu, China.
Int Immunopharmacol. 2025 Feb 6;147:113935. doi: 10.1016/j.intimp.2024.113935. Epub 2025 Jan 4.
Endometrial cancer (EC) is a common gynecological cancer, characterized by increasing incidence and mortality rates. Maackiain (MA), a natural flavonoid compound, has multiple biological activities, but little is known about how it affects EC cells. In the present study, CCK-8, EdU, colony formation, and flow cytometry assays were used to evaluate the effects of MA on EC cell proliferation, apoptosis, and reactive oxygen species (ROS) levels. The effect of MA on autophagy in EC cells were examined through the observation of cell morphology and ultrastructure, and cells were transfected with AdPlus-mCherry-GFP-LC3B for further analysis. Transcriptomic and western blot analyses revealed the underlying mechanism. To evaluate the anti-EC effect of MA in vivo, a xenograft model was established. The results demonstrated that MA inhibited KLE and Ishikawa cell growth in a dose-dependent manner. Furthermore, MA significantly suppressed EC xenograft tumor growth in vivo while exhibiting low toxicity. In addition, EC cells treated with MA exhibited pro-apoptotic and pro-autophagic responses, with the latter exhibiting cytoprotective properties. MA also induced the accumulation of ROS, which promoted endoplasmic reticulum (ER) stress. Notably, the use of the N-acetyl-L-cysteine (NAC) ROS scavenger and the 4-phenylbutyric acid (4-PBA) ER stress inhibitor effectively mitigated the autophagy and apoptosis induced by MA. These results collectively implied that MA triggers autophagy and apoptosis in EC cells through ROS-mediated ER stress, highlighting its potential as a therapeutic agent against EC.
子宫内膜癌（EC）是一种常见的妇科癌症，其发病率和死亡率呈上升趋势。山槐素（MA）是一种天然黄酮类化合物，具有多种生物学活性，但关于它如何影响EC细胞的了解甚少。在本研究中，采用CCK-8、EdU、集落形成和流式细胞术检测来评估MA对EC细胞增殖、凋亡和活性氧（ROS）水平的影响。通过观察细胞形态和超微结构来检测MA对EC细胞自噬的影响，并将细胞用AdPlus-mCherry-GFP-LC3B转染以进行进一步分析。转录组学和蛋白质印迹分析揭示了其潜在机制。为了评估MA在体内的抗EC作用，建立了异种移植模型。结果表明，MA以剂量依赖性方式抑制KLE和Ishikawa细胞生长。此外，MA在体内显著抑制EC异种移植肿瘤生长，同时毒性较低。此外，用MA处理的EC细胞表现出促凋亡和促自噬反应，后者具有细胞保护特性。MA还诱导ROS积累，从而促进内质网（ER）应激。值得注意的是，使用N-乙酰-L-半胱氨酸（NAC）ROS清除剂和4-苯基丁酸（4-PBA）ER应激抑制剂可有效减轻MA诱导的自噬和凋亡。这些结果共同表明，MA通过ROS介导的ER应激触发EC细胞中的自噬和凋亡，突出了其作为抗EC治疗剂的潜力。
