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Anti-Proliferative Effects of Lidocaine as an Autophagy Inducer in Bladder Cancer via Intravesical Instillation: In Vitro and Xenograft Mouse Model Experiments

Authors
 Young Chul Yoo  ;  Na-Young Kim  ;  Seokyung Shin  ;  Yunil Yang  ;  Ji Hae Jun  ;  Ju Eun Oh  ;  Myoung Hwa Kim 
Citation
 CANCERS, Vol.16(7) : 1267, 2024-03 
Journal Title
CANCERS
Issue Date
2024-03
Keywords
Nara Bladder Tumor No. 2 ; anti-tumor effect ; bladder cancer ; lidocaine
Abstract
Lidocaine exerts potential anti-tumor effects on various cancer cell lines, and its intravesical instillation is considered safer than intravenous administration for bladder cancer. However, the mechanisms underlying its anti-tumor effects have not been fully elucidated. Here, we aimed to elucidate the anti-tumor molecular mechanisms of lidocaine in bladder cancer cells and a xenograft model to substantiate the efficacy of its intravesical administration. We investigated the anti-proliferative and autophagyinducing activities of lidocaine in Nara Bladder Tumor No. 2 (NBT-II) rat bladder carcinoma cells using cell viability, flow cytometry, a wound healing assay, and western blotting. We also established a xenograft mouse model of bladder cancer, and cancer growth was examined using in vivo bioluminescence imaging. Lidocaine decreased cell viability, induced G0/G1 phase cell cycle arrest, and inhibited cell migration partially via glycogen synthase kinase (GSK) 3β phosphorylation. Moreover, a combination of lidocaine and SB216763 (a GSK3β inhibitor) suppressed autophagy-related protein expression. Bafilomycin-A1 with lidocaine significantly enhanced microtubule-associated protein 1A/1B-light chain (LC3B) expression; however, it decreased LC3B expression in combination with 3-methyladenine compared to lidocaine alone. In the xenograft mouse model, the bladder cancer volume was reduced by lidocaine. Overall, lidocaine exerts anti-proliferative effects on bladder cancer via an autophagy-inducing mechanism.
Files in This Item:
T202402190.pdf Download
DOI
10.3390/cancers16071267
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Na Young(김나영) ORCID logo https://orcid.org/0000-0003-3685-2005
Kim, Myoung Hwa(김명화) ORCID logo https://orcid.org/0000-0003-4723-9425
Shin, Seokyung(신서경) ORCID logo https://orcid.org/0000-0002-2641-0070
Yoo, Young Chul(유영철) ORCID logo https://orcid.org/0000-0002-6334-7541
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198880
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