Ivermectin Inhibits Bladder Cancer Cell Growth and Induces Oxidative Stress and DNA Damage
Ning Fan1, Lixiu Zhang2, Zhiping Wang1
1Institute of Urology, Key Laboratory of Gansu Urological Diseases, Gansu Nephro-Urological Clinical Center, Department of Urology, Lanzhou University Second Hospital, Lanzhou, 730030, China.
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 in vitro and in vivo.
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 in vivo.
Results:
Our study showed that in vitro and in vivo, 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.
Insights
Ivermectin, an anti-parasitic drug, effectively inhibits bladder cancer cell growth both in vitro and in vivo. This study demonstrates its potential as a novel therapeutic agent by inducing apoptosis and DNA damage in cancer cells.
Area of Science:
- Oncology
- Pharmacology
- Urology
Background:
- Bladder cancer is a prevalent urinary system malignancy with limited therapeutic options.
- Novel treatment strategies are urgently needed for effective bladder cancer management.
Purpose of the Study:
- To investigate the anti-cancer effects of Ivermectin, a broad-spectrum anti-parasitic agent, on bladder cancer.
- To evaluate Ivermectin's efficacy both in vitro and in vivo.
Main Methods:
- Cell proliferation was assessed using CCK-8 and EdU assays.
- Apoptosis, reactive oxygen species (ROS) levels, and DNA damage were analyzed via flow cytometry, TUNEL assay, Western blotting, and Comet assay.
- Xenograft tumor models in nude mice were utilized for in vivo evaluation.
Main Results:
- Ivermectin demonstrated significant inhibition of bladder cancer cell growth in vitro and in vivo.
- Ivermectin induced apoptosis, increased ROS production, and caused DNA damage in bladder cancer cells.
- The ATM/P53 pathway-related proteins were activated by Ivermectin treatment.
Conclusions:
- Ivermectin exhibits potent anti-cancer properties against bladder cancer.
- Ivermectin shows promise as a potential therapeutic candidate for bladder cancer treatment.
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