Antitumor effects of valdecoxib on hypopharyngeal squamous carcinoma cells

Korean J Physiol Pharmacol. 2022 Nov 1;26(6):439-446. doi: 10.4196/kjpp.2022.26.6.439.

Abstract

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effects of valdecoxib (Val), an United States Food and Drug Administration-approved anti-inflammatory drug that was withdrawn due to the side effects of increased risk of cardiovascular adverse events, were investigated in hypopharyngeal squamous cell carcinoma cells by performing a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 μM 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 α4/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.

Keywords: Apoptosis; Hypopharyngeal squamous cell carcinoma; Integrin α4/FAK signaling; MAPK pathway; Valdecoxib.