title: Tolfenamic Acid Inhibits the Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma: Involvement of p38-Mediated Down-Regulation of Slug.
abstract: OBJECTIVE
  Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to exhibit antitumor effects in various cancers apart from nasopharyngeal cancer (NPC). NPC exhibits high invasiveness, as well as metastatic potential, and patients continue to suffer from residual, recurrent, or metastatic disease even after chemoradiation therapy. Therefore, new treatment strategies are needed for NPC. In this study, we investigated the efficacy and molecular mechanisms of TA in NPC treatment.
  
  
  METHODS
  TA-induced cell death was detected by cell viability assay in the NPC cell lines, HNE1 and HONE1. Wound healing assay, invasion assay, and Western blot analysis were used to evaluate the antitumor effects of TA in NPC cell lines.
  
  
  RESULTS
  Treatment with TA suppressed the migration and invasion of HNE1 and HONE1 cells. Hepatocyte growth factor enhanced the proliferation, migration, and invasion abilities of NPC cells. This enhancement was successfully inhibited by TA treatment. Treatment with TA increased phosphorylation of p38, and the inhibition of p38 with SB203580 reversed the cytotoxic, anti-invasive, and anti-migratory effects of TA treatment in NPC cell lines. Moreover, inhibition of p38 also reversed the decrease in expression of Slug that was induced by TA treatment.
  
  
  CONCLUSIONS
  In conclusion, the activation of p38 plays a role in mediating TA-induced cytotoxicity and inhibition of invasion and migration via down-regulation of Slug.
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.|Center of Excellent in Otorhinolaryngology, Head and Neck Surgery, Rajavithi Hospital, Bangkok, Thailand.
authors.forename: Tatsanachat
authors.initials: T
authors.lastname: Jittreetat
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Korea.
authors.forename: Bok-Soon
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Yeon Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Center of Excellent in Otorhinolaryngology, Head and Neck Surgery, Rajavithi Hospital, Bangkok, Thailand. drpackdee@gmail.com.
authors.forename: Phakdee
authors.initials: P
authors.lastname: Sannikorn
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Korea. ostium@ajou.ac.kr.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D015536:Down-Regulation; D049851:Gastropoda; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles; D020935:MAP Kinase Signaling System / Q000187:drug effects; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines; D062367:ortho-Aminobenzoates / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C066855:HGF protein, human; D007093:Imidazoles; D011725:Pyridines; D062367:ortho-Aminobenzoates; C009500:tolfenamic acid; D017228:Hepatocyte Growth Factor; C093642:SB 203580
keywords: Slug; Tolfenamic acid; nasopharyngeal cancer; p38 mitogen-activated protein kinase