PPARγ‐mediated antineoplastic effect of NSAID sulindac on human oral squamous carcinoma cells

作者: Nikolaos G. Nikitakis , Carla Hebert , Marcio A. Lopes , Mark A. Reynolds , John J. Sauk

DOI: 10.1002/IJC.10278

关键词:

摘要: There is strong evidence that nonsteroidal antiinflammatory drug (NSAID) sulindac may exert a significant antineoplastic effect. The purpose of our study was to explore the effects on human oral squamous cell carcinoma (SCCa) cells and elucidate underlying molecular mechanisms. changes treatment induced growth, apoptosis cycle distribution SCCa lines were assessed by growth flow cytometry experiments. Utilizing quantitative RT-PCR immunocytochemistry, we determined effect mRNA protein expression different sulindac's targets. Also, PPARγ selectively targeted antisense oligonucleotide treatment. Both sulfide sulfone metabolites sulindac, which differ in ability cause COX-2 inhibition, dose- time-dependent reduction accompanied increase without concomitant arrest. Sulindac also caused upregulation levels PPARs. Treatment with oligonucleotides abolished inhibitory Our results are consistent NSAID cells, mediated, at least partially, through induction apoptosis. We suggest activation be, responsible for antiproliferative © 2002 Wiley-Liss, Inc.

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