Xiong Chenyi, Tang Yining, Li Feng, Ye Yang, Li Xiaoran, Lin Jinxing, Dai Sunxian
Department of Thoracic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212000, P.R. China.
Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Oncol Lett. 2024 May 28;28(2):339. doi: 10.3892/ol.2024.14473. eCollection 2024 Aug.
3,3'-Diindolylmethane (DIM) is a natural phytochemical derived from cruciferous plants that has inhibitory effects on a wide range of tumor cells; however, its relevant effects on esophageal cancer cells have been poorly studied. Therefore, in the present study, a pharmacology network approach was used to predict the possible core targets of DIM acting on esophageal cancer. Subsequently, using experiments, TE-1 human esophageal cancer cells were treated with different concentrations of DIM (0, 40, 60 and 80 µM) for 24 h. Changes in cell activity were detected by Cell Counting Kit-8 assay, and changes in the expression levels of stromal interaction molecule 1 (STIM1) and apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2) and Bax, were assessed by western blotting, followed by the upregulation of STIM1 by thapsigargin (Tg). Network pharmacology analysis showed that there were 39 potential core targets of DIM in esophageal cancer. The results of the experiments showed that DIM could inhibit the viability of esophageal cancer cells, downregulate the expression of STIM1 and Bcl-2 proteins and upregulate the expression of Bax protein, all in a concentration-dependent manner. The results also demonstrated that toxic carotenoids were agonist against STIM1 protein and upregulated STIM1 and Bax protein expression. After agonizing STIM1 protein expression using Tg, DIM was able to counteract the expression trend of STIM1, Bcl-2 and Bax protein in TE-1 cells. In summary, DIM induced apoptosis and inhibited the viability of esophageal cancer cells by downregulating the expression of STIM1 protein; therefore, the natural phytochemical, DIM, may be a potential substance for the early prevention and treatment of esophageal cancer cells.
3,3'-二吲哚甲烷（DIM）是一种源自十字花科植物的天然植物化学物质，对多种肿瘤细胞具有抑制作用；然而，其对食管癌细胞的相关作用研究较少。因此，在本研究中，采用药理学网络方法预测DIM作用于食管癌的可能核心靶点。随后，通过实验，用不同浓度的DIM（0、40、60和80μM）处理TE-1人食管癌细胞24小时。采用细胞计数试剂盒-8法检测细胞活性变化，通过蛋白质免疫印迹法评估基质相互作用分子1（STIM1）及凋亡相关蛋白B细胞淋巴瘤-2（Bcl-2）和Bax表达水平的变化，随后用毒胡萝卜素（Tg）上调STIM1表达。网络药理学分析表明，DIM在食管癌中有39个潜在核心靶点。实验结果表明，DIM可抑制食管癌细胞活力，下调STIM1和Bcl-2蛋白表达并上调Bax蛋白表达，且均呈浓度依赖性。结果还表明，毒性类胡萝卜素是STIM1蛋白的激动剂，可上调STIM1和Bax蛋白表达。用Tg激动STIM1蛋白表达后，DIM能够抵消TE-1细胞中STIM1、Bcl-2和Bax蛋白的表达趋势。综上所述，DIM通过下调STIM1蛋白表达诱导食管癌细胞凋亡并抑制其活力；因此，天然植物化学物质DIM可能是早期预防和治疗食管癌细胞的潜在物质。
