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Nitidine chloride regulates cell function of bladder cancer in vitro through downregulating Lymphocyte antigen 75

Nitidine chloride (NC) is effective on cancer in many tumors, but its effect on bladder cancer (BC) is unknown. We conducted cell function experiments to verify the antineoplastic effect of NC on BC cell lines (5637, T24, and UM-UC-3) in vitro. Then, mRNAs of NC-treated and NC-untreated BC cells wer...

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Published in:Naunyn-Schmiedeberg's archives of pharmacology 2023-09, Vol.396 (9), p.2071-2085
Main Authors: Wang, Shi-shuo, Zhai, Gao-qiang, Huang, Zhi-guang, Luo, Jia-yuan, He, Juan, Huang, Jie-zhuang, Yang, Ling, Xiao, Chu-nan, Li, Su-li, Chen, Kai-rong, Chen, Yan-yu, Ji, Han-chu, Ding, Jun-ping, Li, Sheng-hua, Cheng, Ji-wen, Chen, Gang
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Language:English
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Summary:Nitidine chloride (NC) is effective on cancer in many tumors, but its effect on bladder cancer (BC) is unknown. We conducted cell function experiments to verify the antineoplastic effect of NC on BC cell lines (5637, T24, and UM-UC-3) in vitro. Then, mRNAs of NC-treated and NC-untreated BC cells were extracted for mRNA sequencing. Differentially expressed genes (DEGs), expression analysis, and drug molecular docking were conducted to discover the target gene of NC. Finally, functional enrichment was analyzed to explore the underlying mechanisms. NC dramatically inhibited proliferation, migration, and invasion, and it induced apoptosis and arrested the S and G2/M phases of BC cell lines. Lymphocyte antigen 75 (LY75) appeared to be the target of NC. LY75 was highly expressed and had the ability to distinguish BC tissue from non-cancerous tissue. Then, drug molecular docking confirmed the targeting relationship between NC and LY75. Gene enrichment analysis showed that the downregulated genes, after being treated with NC, were mainly enriched in pathways relevant to cell pathophysiological processes. NC inhibits BC cell proliferation, migration, and invasion, induces apoptosis, and arrests cell cycles by downregulating the expression of LY75. This study provides molecular and theoretical bases for NC treatment of BC.
ISSN:0028-1298
1432-1912
DOI:10.1007/s00210-023-02446-0