KMID : 0811720220260060439
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Korean Journal of Physiology & Pharmacology 2022 Volume.26 No. 6 p.439 ~ p.446
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Antitumor effects of valdecoxib on hypopharyngeal squamous carcinoma cells
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Trang Nguyen Thi Kieu
Yoo Hoon
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Abstract
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The antitumoral effects of valdecoxib (Val), an United States Food and Drug Administration-approved anti-inflammatory drug that was withdrawn due to the side effects of increased risk of cardiovascular adverse events, were investigated in hypopharyngeal squamous cell carcinoma cells by performing a cell viability assay, transwell assay, immunofluorescence imaging, and Western blotting. Val markedly inhibited cell viability with an IC50 of 67.3 ¥ìM after 48 h of treatment, and also downregulated cell cycle proteins such as Cdks and their regulatory cyclin units. Cell migration and invasion were severely suppressed by inhibiting integrin ¥á4/FAK expression. In addition, Val activated the cell cycle checkpoint CHK2 in response to excessive DNA damage, which led to the activation of caspase-3/9 and induced caspase-dependent apoptosis. Furthermore, the signaling cascades of the PI3K/AKT/mTOR and mitogen-activated protein kinase pathways were significantly inhibited by Val treatment. Taken together, our results indicate that Val can be used for the treatment of hypopharyngeal squamous cell carcinoma.
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KEYWORD
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Apoptosis, Hypopharyngeal squamous cell carcinoma, Integrin ¥á4/FAK signaling, MAPK pathway, Valdecoxib.
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