伊维菌素抑制膀胱癌细胞生长并诱导氧化应激和 DNA 损伤。
Ivermectin Inhibits Bladder Cancer Cell Growth and Induces Oxidative Stress and DNA Damage.
机构信息
Institute of Urology, Key Laboratory of Gansu Urological Diseases, Gansu Nephro-Urological Clinical Center, Department of Urology, Lanzhou University Second Hospital, Lanzhou, 730030, China.
Department of Clinical Laboratory, Maternal and Child Health Hospital of Gansu. Lanzhou, 730050, China.
出版信息
Anticancer Agents Med Chem. 2024;24(5):348-357. doi: 10.2174/0118715206274095231106042833.
BACKGROUND
Bladder cancer is the most common malignant tumor of the urinary system. Nevertheless, current therapies do not provide satisfactory results. It is imperative that novel strategies should be developed for treating bladder cancer.
OBJECTIVES
To evaluate the effect of a broad-spectrum anti-parasitic agent, Ivermectin, on bladder cancer cells and .
METHODS
CCK-8 and EdU incorporation assays were used to evaluate cell proliferation. Apoptosis was detected by flow cytometry, TUNEL assay, and western blotting. Flow cytometry and DCFH-DA assay were used to analyze the reactive oxygen species (ROS) levels. DNA damage was determined by Neutral COMET assay and γ H2AX expression. Proteins related to apoptosis and DNA damage pathways were determined by WB assay. Xenograft tumor models in nude mice were used to investigate the anti-cancer effect of Ivermectin .
RESULTS
Our study showed that and , Ivermectin inhibited the growth of bladder cancer cells. In addition, Ivermectin could induce apoptosis, ROS production, DNA damage, and activate ATM/P53 pathwayrelated proteins in bladder cancer cells.
CONCLUSIONS
According to these findings, Ivermectin may be a potential therapeutic candidate against bladder cancer due to its significant anti-cancer effect.
背景
膀胱癌是泌尿系统最常见的恶性肿瘤。然而，目前的治疗方法并不能提供满意的结果。因此，迫切需要开发治疗膀胱癌的新策略。
目的
评估广谱抗寄生虫药物伊维菌素对膀胱癌细胞的作用。
方法
CCK-8 和 EdU 掺入实验用于评估细胞增殖。通过流式细胞术、TUNEL 检测和 Western blot 检测评估细胞凋亡。通过流式细胞术和 DCFH-DA 实验检测活性氧（ROS）水平。通过中性彗星实验和 γ H2AX 表达检测 DNA 损伤。通过 WB 实验检测与细胞凋亡和 DNA 损伤途径相关的蛋白。使用裸鼠皮下移植瘤模型研究伊维菌素的抗癌作用。
结果
本研究表明，伊维菌素能够显著抑制膀胱癌 T24 和 5637 细胞的生长。此外，伊维菌素能够诱导膀胱癌细胞凋亡、ROS 产生、DNA 损伤，并激活 ATM/P53 通路相关蛋白。
结论
根据这些发现，伊维菌素可能因其显著的抗癌作用而成为治疗膀胱癌的潜在候选药物。
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