Liu Yanfeng, Zhang Ming
Department of General Surgery, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China.
Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China.
J Biochem Mol Toxicol. 2025 Apr;39(4):e70237. doi: 10.1002/jbt.70237.
In the current period of pharmaceutical discovery, herbal remedies have shown to be an unmatched supply of anticancer medications. By changing the tumor microenvironment and several signaling pathways, plants and their byproducts through analogs have an important part in the therapy for carcinoma. The current investigation assessed the effectiveness of inhibiting the development of gastric cancer cells in HGC-27 cells by attenuating the PI3K/AKT and ERK 1/2 MAPK signaling pathways using the natural medicines silibinin (SIL) and sulforaphane (SFN) complemented by molecular docking analysis. After being exposed to various doses of SIL and SFN (SIL+SFN) for 24 h (0-50 µM), the cells were evaluated for multiple studies. The MTT assay was used to examine the combo that SIL+SFN induced cytotoxicity. ROS was assessed by DCFH-DA staining. Apoptotic changes were investigated, and MMP levels in HGC-27 cells were investigated utilizing the proper fluorescent staining techniques. Flow cytometry and western blot analysis were used to evaluate the protein profiles of cell survival, cell cycle, proliferation, and apoptosis. The molecular docking was conducted with Autodock Vina (v1.5.6). The docking results were analyzed using BIOVIA Discovery Studio Visualizer to identify key interactions. The relative cytotoxicity of SIL and SFN was found to be approximately 24.96 and 28.79 μM, correspondingly, according to the findings. After a 24-h incubation period, the combination of SIL and SFN generates significant cytotoxicity in HGC-27 cells, with an IC of 15.43 μM. Furthermore, HGC-27 cells administered SIL and SFN simultaneously exhibited elevated apoptotic signals and significant ROS production. Molecular docking demonstrated strong binding affinities between the compounds and the target proteins, supporting their potential mechanisms of action. Therefore, the combination usage of SIL + SFN has been viewed as a chemotherapeutic drug since it prevents the synthesis of PI3K/AKT and ERK 1/2 MAPK mediated control of cell growth and cell cycle-regulating proteins. To utilize them commercially conducting more in vivo research in the near future will be necessary to ascertain how well the co-treatment triggers apoptosis.
在当前的药物研发阶段，草药已被证明是抗癌药物的一个无与伦比的来源。通过改变肿瘤微环境和多种信号通路，植物及其通过类似物产生的副产品在癌症治疗中发挥着重要作用。当前的研究使用天然药物水飞蓟宾（SIL）和萝卜硫素（SFN），并辅以分子对接分析，评估通过减弱PI3K/AKT和ERK 1/2 MAPK信号通路来抑制HGC-27细胞中胃癌细胞生长的有效性。在暴露于不同剂量的SIL和SFN（SIL+SFN）24小时（0-50μM）后，对细胞进行多项研究评估。MTT法用于检测SIL+SFN联合诱导的细胞毒性。通过DCFH-DA染色评估活性氧（ROS）。研究凋亡变化，并利用适当的荧光染色技术研究HGC-27细胞中的线粒体膜电位（MMP）水平。流式细胞术和蛋白质印迹分析用于评估细胞存活、细胞周期、增殖和凋亡的蛋白质谱。使用Autodock Vina（v1.5.6）进行分子对接。使用BIOVIA Discovery Studio Visualizer分析对接结果以确定关键相互作用。根据研究结果，发现SIL和SFN的相对细胞毒性分别约为24.96和28.79μM。在24小时的孵育期后，SIL和SFN的组合在HGC-27细胞中产生显著的细胞毒性，半数抑制浓度（IC）为15.43μM。此外，同时给予SIL和SFN的HGC-27细胞表现出升高的凋亡信号和显著的ROS产生。分子对接表明化合物与靶蛋白之间具有很强的结合亲和力，支持了它们潜在的作用机制。因此，SIL+SFN的联合使用被视为一种化疗药物，因为它可阻止PI3K/AKT和ERK 1/2 MAPK介导的细胞生长控制和细胞周期调节蛋白的合成。为了将它们商业化使用，在不久的将来有必要进行更多的体内研究，以确定联合治疗引发凋亡的效果如何。
