두경부편평세포암종에서 Gleevec의 효과

• 영문명: Effect of Gleevec on Head and Neck Squamous Cell Carcinoma
• 발행기관: 대한두경부종양학회
• 저자명: 주형로(Hyung Ro Chu) Robert A Weisman
• 간행물 정보: 『대한두경부종양학회지』제21권 제2호, 158~164쪽, 전체 7쪽
• 주제분류: 의약학 > 종양학
• 파일형태: PDF
• 발행일자: 2005.11.30

영문 초록

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 6μM 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.

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대상 및 방법

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키워드

타이로신키나제 두경부악성종양 Akt Tyrosine kinase Serine threonine kinase Head and neck cancer