Antitumor effects of valdecoxib on hypopharyngeal squamous carcinoma cells
Nguyen Thi Kieu Trang1,2 and Hoon Yoo1,*
1Department of Pharmacology and Dental Therapeutics, College of Dentistry, Chosun University, Gwangju 61452, Korea, 2Department of Pharmacy, Thai Binh University of Medicine and Pharmacy, Thai Binh City 06000, Vietnam
Author contributions: All experiments were conducted by N.T.K.T. under the supervision of Prof. H.Y. Authors have participated in editing and revising the manuscript.
Received: February 25, 2022; Revised: July 5, 2022; Accepted: July 18, 2022
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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effects of valdecoxib (Val), an United States Food and Drug Administration-approved anti-inflammatory drug that was withdrawn due to the side effects of increased risk of cardiovascular adverse events, were investigated in hypopharyngeal squamous cell carcinoma cells by performing a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.