Han Li, Li Peiwu, Fu Xu, Huang Zhenzhen, Yin Wen
Key Laboratory of Emergency Medicine, Lanzhou University Second Hospital, Lanzhou, China.
Department of Pharmacy, Lanzhou University Second Hospital, Lanzhou, China.
Anticancer Agents Med Chem. 2023;23(4):478-487. doi: 10.2174/1871520622666220615142636.
Aesculetin (AE), a natural coumarin derivative found in traditional medicinal herbs, has a variety of pharmacological effects. However, the role of AE and its molecular mechanisms of action on bladder cancer remains undefined.
The study aims to explore the anti-tumor effects of AE on bladder cancer cells and the associated molecular mechanisms.
We performed a Cell Counting Kit-8 assay to examine the inhibitory effects of AE on 5637 and T24 cells. The anti-tumor effects of AE on 5637 cells were evaluated by performing colony formation, living/dead cell staining, apoptosis, cell cycle, migration and invasion assays. The expression levels of related proteins were determined using western blotting.
The viability of 5637 and T24 cells was decreased by AE. AE significantly inhibited colony formation, arrested the cell cycle at the G0/G1 phase, decreased migration and invasion, decreased the mitochondrial membrane potential and increased apoptosis in 5637 cells. Western blotting results showed the release of cytochrome C from mitochondria; the activation of caspase-9 and caspase-3; decrease in CDK4, CCND1, MMP2 and MMP9 levels and an increase in the BAX/BCL-2 protein ratio after treatment with AE. AE also downregulated the levels of p-ERK and p- MEK proteins. Pre-treatment with U0126 significantly enhanced the anti-tumor effects of AE.
AE inhibited the proliferation and induced the apoptosis of bladder cancer cells through the MEK/ERK pathway. These findings provide possible therapeutic strategies for bladder cancer.
七叶亭（AE）是一种存在于传统草药中的天然香豆素衍生物，具有多种药理作用。然而，AE对膀胱癌的作用及其分子作用机制尚不清楚。
本研究旨在探讨AE对膀胱癌细胞的抗肿瘤作用及其相关分子机制。
我们使用细胞计数试剂盒-8检测AE对5637和T24细胞的抑制作用。通过集落形成、活/死细胞染色、凋亡、细胞周期、迁移和侵袭实验评估AE对5637细胞的抗肿瘤作用。使用蛋白质印迹法测定相关蛋白的表达水平。
AE降低了5637和T24细胞的活力。AE显著抑制5637细胞的集落形成，使细胞周期停滞在G0/G1期，减少迁移和侵袭，降低线粒体膜电位并增加凋亡。蛋白质印迹结果显示线粒体中细胞色素C的释放；caspase-9和caspase-3的激活；用AE处理后，CDK4、CCND1、MMP2和MMP9水平降低，BAX/BCL-2蛋白比率增加。AE还下调了p-ERK和p-MEK蛋白的水平。用U0126预处理显著增强了AE的抗肿瘤作用。
AE通过MEK/ERK途径抑制膀胱癌细胞的增殖并诱导其凋亡。这些发现为膀胱癌提供了可能的治疗策略。
