Korean Journal of Head & Neck Oncology (대한두경부종양학회지)

The Korean Society for Head and Neck Oncology (대한두경부종양학회)
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Effect of Gleevec on Head and Neck Squamous Cell Carcinoma

두경부편평세포암종에서 Gleevec의 효과

  • Chu Hyung-Ro (Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine) ;
  • Weisman Robert A. (Department of Surgery, Division of Head and Neck Surgery, University of California)
  • 주형로 (한림대학교 의과대학 이비인후-두경부외과학교실) ;
  • Published : 2005.11.01
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Abstract

Purpose: The serine/threonine kinase Akt was described to inhibit apoptosis in cancer. This study was to examine the effect of Gleevec on head and neck squamous cell carcinoma(HNSCC) through the mechanism of Akt. Experimental Design: Gleevec was introduced into the HNSCC cell lines UMSCC10B, HN12 and HN30 in a range of concentrations. Cell viability was assessed by clonogenic survival analysis. Targets of Gleevec(PDGFR, c-Kit, and c-Abl) were evaluated by Western blot. HNSCC tissue samples were stained for PDGFR, c-Kit and phosphorylated Akt. Akt phosphorylation following Gleevec treatment was assessed using Western blot. Akt siRNA was used to as the positive control. Results: Colony forming efficiency decreased with an increase in concentration of Gleevec. Expressions of PDGFR, c-Kit, and c-Abl were observed in HNSCC cells. Immunohistochemistry confirmed high expression of PDGFR, c-Kit, and p-Akt in human HNSCC tissues. Akt kinase activity was significantly inhibited with increasing concentration of Gleevec in HNSCC cells, and near complete dephosphorylation of Akt was observed at $6{\mu}M$ of Gleevec in the UMSCC10B and HN30 cell lines. Conclusions: Gleevec at clinically comparable concentrations caused a dose dependant decrease in HNSCC survival. The decreased cell survival was related to the inhibition of Akt kinase activity and dephosphorylation of Akt. Akt signaling pathway may be a relevant target for Gleevec in treating HNSCC.

Keywords

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