Anti-cancer effects of celecoxib in head and neck carcinoma.
Although many studies highlighted cyclooxygenase2 (COX2) inhibition as a promising therapeutic strategy for cancer, more evidence is needed for clinical application. The purpose of this study was to investigate the feasibility of COX2 inhibition as a strategic treatment modality for head and neck carcinoma (HNC). We tested COX2 inhibitor, celecoxib in six types of HNC cells and analyzed the expression changes in proteins related to angiogenesis and apoptosis in vitro. We also evaluated proliferation, gelatinolysis and in vitro invasion. We used a hamster carcinogenesis model and a mouse tumorigenesis model for the in vivo evaluation of COX2 inhibition. We performed immunohistochemistry to assess changes in the expression of COX2, survivin and angiogenesis. Celecoxib administration caused decreases in the expressions of COX2, VEGF and survivin in vitro. Proliferation, in vitro invasion and gelatinolytic activity were reduced in HNC cell lines, but the effect was inconsistent across lines. COX2 inhibition retarded oral carcinogenesis from an early carcinogenic stage with increased apoptosis and decreased survivin expression. COX2 inhibition did not inhibit tumor growth, even with the COX2 downregulation and decrease in neovascularization. We conclude that COX2 inhibition has a chemopreventive effect, but its application as a treatment of HNC in a clinical setting still requires further research to overcome its limited anti-cancer effects.
Kim
Young-Youn
YY
Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul 110-749, Korea.
Lee
Eun-Jin
EJ
Kim
Yu-Kyoung
YK
Kim
Soung-Min
SM
Park
Ju-Yong
JY
Myoung
Hoon
H
Kim
Myung-Jin
MJ
D000818:Animals; D000068579:Celecoxib; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018890:Chemoprevention; D006224:Cricetinae; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
C107489:BIRC5 protein, human; D016861:Cyclooxygenase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D000077022:Survivin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib