Ivermectin Inhibits Bladder Cancer Cell Growth and Induces Oxidative Stress and DNA Damage


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Abstract

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.

Objective: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.

Conclusion:According to these findings, Ivermectin may be a potential therapeutic candidate against bladder cancer due to its significant anti-cancer effect.

About the authors

Ning Fan

Institute of Urology, Key Laboratory of Gansu Urological Diseases, Gansu Nephro-Urological Clinical Center, Department of Urology, Lanzhou University Second Hospital

Email: info@benthamscience.net

Lixiu Zhang

Department of Clinical Laboratory,, Gansu Provincial Maternal and Child Health Hospital

Email: info@benthamscience.net

Zhiping Wang

Institute of Urology, Key Laboratory of Gansu Urological Diseases, Gansu Nephro-Urological Clinical Center, Department of Urology, Lanzhou University Second Hospital

Author for correspondence.
Email: info@benthamscience.net

Hui Ding

Institute of Urology, Key Laboratory of Gansu Urological Diseases, Gansu Nephro-Urological Clinical Center, Department of Urology, Lanzhou University Second Hospital

Author for correspondence.
Email: info@benthamscience.net

Zhongjin Yue

Institute of Urology, Key Laboratory of Gansu Urological Diseases, Gansu Nephro-Urological Clinical Center, Department of Urology, Lanzhou University Second Hospital

Author for correspondence.
Email: info@benthamscience.net

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