Ji Mingming, Sun Jian, Zhao Jun
Department of Thoracic Surgery, 74566The First Affiliated Hospital of Soochow University, Jiangsu, China.
The First People's Hospital of Yancheng, 38044The Yancheng Clinical College of Xuzhou Medical University, Jiangsu, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221127429. doi: 10.1177/09603271221127429.
As an aggressive human malignancy, esophageal squamous cell carcinoma (ESCC) is prevalent globally, especially in China. Verbascoside (VE) exerts anti-cancer effects in several human cancers. This work was to investigate the effects of VE on ESCC cells.
Esophageal squamous cell carcinoma cell proliferation, apoptosis, migration, and invasion were assessed by CCK-8, TUNEL, and Transwell assays. Gene and protein levels were detected by RT-qPCR and western blotting. CDC42 activity was evaluated by G-lisa assay.
Verbascoside significantly inhibited cell proliferation, migration, and invasion and induced cell apoptosis in ESCC cells. Furthermore, it was found that VE markedly inhibited HMGB1 and RAGE expression in a dose-dependent manner. Besides, HMGB1/RAGE upregulation partially reversed the anti-cancer effects of VE on ESCC cells. VE repressed HMGB1/RAGE-induced CDC42 activation in ESCC cells. In addition, ML141-mediated CDC42 inactivation further enhanced the effect of VE on ESCC cell proliferation, apoptosis, migration, and invasion.
Our findings indicated that VE has significant anti-tumor potential in ESCC by suppressing HMGB1/RAGE-dependent CDC42 activation.
食管鳞状细胞癌（ESCC）作为一种侵袭性人类恶性肿瘤，在全球范围内普遍存在，尤其是在中国。毛蕊花糖苷（VE）在几种人类癌症中发挥抗癌作用。本研究旨在探讨VE对ESCC细胞的影响。
采用CCK-8、TUNEL和Transwell实验评估食管鳞状细胞癌细胞的增殖、凋亡、迁移和侵袭能力。通过RT-qPCR和蛋白质印迹法检测基因和蛋白质水平。采用G-lisa实验评估CDC42活性。
毛蕊花糖苷显著抑制ESCC细胞的增殖、迁移和侵袭，并诱导细胞凋亡。此外，发现VE以剂量依赖性方式显著抑制HMGB1和RAGE的表达。此外，HMGB1/RAGE上调部分逆转了VE对ESCC细胞的抗癌作用。VE抑制ESCC细胞中HMGB1/RAGE诱导的CDC42激活。此外，ML141介导的CDC42失活进一步增强了VE对ESCC细胞增殖、凋亡、迁移和侵袭的作用。
我们的研究结果表明，VE通过抑制HMGB1/RAGE依赖的CDC42激活在ESCC中具有显著的抗肿瘤潜力。
