Yonsei Med J.  2016 May;57(3):588-598. 10.3349/ymj.2016.57.3.588.

Tolfenamic Acid Inhibits the Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma: Involvement of p38-Mediated Down-Regulation of Slug

Affiliations
  • 1Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea. ostium@ajou.ac.kr
  • 2Center of Excellent in Otorhinolaryngology, Head and Neck Surgery, Rajavithi Hospital, Bangkok, Thailand. drpackdee@gmail.com
  • 3Department of Molecular Science and Technology, Ajou University, Suwon, Korea.

Abstract

PURPOSE
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.
MATERIALS AND 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.
CONCLUSION
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.

Keyword

Tolfenamic acid; nasopharyngeal cancer; p38 mitogen-activated protein kinase; Slug

MeSH Terms

Animals
Anti-Inflammatory Agents, Non-Steroidal/*pharmacology/therapeutic use
Cell Line, Tumor
Cell Movement/*drug effects
Cell Proliferation/*drug effects
Cell Survival/*drug effects
Down-Regulation
Gastropoda
Gene Expression Regulation, Neoplastic/drug effects
Hepatocyte Growth Factor/metabolism/*pharmacology
Humans
Imidazoles
MAP Kinase Signaling System/drug effects
Nasopharyngeal Neoplasms/*drug therapy/metabolism/pathology
Neoplasm Invasiveness/*prevention & control
Phosphorylation/drug effects
Pyridines
ortho-Aminobenzoates/*pharmacology/therapeutic use
Anti-Inflammatory Agents, Non-Steroidal
Hepatocyte Growth Factor
Imidazoles
Pyridines
ortho-Aminobenzoates
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