Etodolac, a selective cyclo-oxygenase-2 inhibitor, enhances carboplatin-induced apoptosis of human tongue carcinoma cells by down-regulation of FAP-1 expression.
The human tongue well-differentiated squamous carcinoma cell line, SCC-25, shows Fas-dependent apoptosis by treatment with carboplatin (CBDCA). FADD is markedly up-regulated by CBDCA, resulting in the induction of apoptosis. FAP-1, antiapoptotic tyrosine phosphatase, is expressed in the cytosol and blocks the transduction of the "death signal" from Fas to downstream. In this study, we show that etodolac, a selective cyclo-oxygenase-2 inhibitor, enhanced CBDCA-induced apoptosis of SCC-25, although etodolac alone did not induce the apoptosis. In combination with CBDCA, etodolac significantly decreased FAP-1 expression both at protein and mRNA levels, although etodolac by itself did not inhibit FAP-1 expression. These results indicate that etodolac, when combined with CBDCA, can enhance an action of anticancer drug through the suppression of FAP-1 expression.
Mishima
Koichi
K
Department of Oral and Maxillofacial Surgery, Shimane University School of Medicine, Izumo, Shimane 693-8501, Japan. omfs3@med.shimane-u.ac.jp
Nariai
Yoshiki
Y
Yoshimura
Yasuro
Y
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016190:Carboplatin / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D017308:Etodolac / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D016861:Cyclooxygenase Inhibitors; D009363:Neoplasm Proteins; D017308:Etodolac; D016190:Carboplatin; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases