계명대학교 의학도서관 Repository

Tumor Growth Inhibition by Simultaneously Blocking Epidermal Growth Factor Receptor and Cyclooxygenase-2 in a Xenograft Model

Metadata Downloads
Author(s)
Xin ZhangZhuo (Georgia) ChenMi Sun ChoeYan LinShi-Yong SunH. Samuel WieandHyung Ju C. ShinAmy ChenFadlo R. KhuriDong M. Shin
Keimyung Author(s)
Choe, Mi Sun
Department
Dept. of Pathology (병리학)
Journal Title
Clinical Cancer Research
Issued Date
2005
Volume
11
Issue
17
Abstract
Purpose: Our previous study revealed that simultaneously targeting epidermal growth factor receptor (EGFR) tyrosine kinase and cyclooxygenase-2 (COX-2) additively or synergistically inhibited growth of squamous cell carcinoma of the head and neck (SCCHN) in vitro. However, an in vivo efficacy of this combined treatment in SCCHN has not been studied.

Experimental Design: Nude mice were pretreated with control (1% Tween 80), ZD1839 (50 mg/kg) alone, celecoxib (50 mg/kg) alone, or a combination of ZD1839 and celecoxib at the same dosages for 7 days before injection of a human SCCHN cell line Tu212. The animals were continuously treated with the agents 5 days a week for about 11 weeks.

Results: Tumor growth in the combined treatment was significantly inhibited compared with the control (P < 0.001), ZD1839 (P = 0.005), or celecoxib (P < 0.001). At the same time, a dramatic delay of tumor progression was observed in the combined treatment compared with all other three groups. Molecular analysis showed that the combined treatment significantly decreased prostaglandin E metabolite production. The cooperative effect of these two agents in combination was also associated with down-regulation of phosphorylated EGFR, phosphorylated extracellular signal-regulated kinase, and phosphorylated signal transducers and activators of transcription 3 levels and reduction of vascular endothelial growth factor and Ki-67 expression. Specifically, gene silencing of both EGFR and COX-2 by small interfering RNA further confirmed the cooperative antitumor effect.

Conclusion: The current results strongly suggest that a cooperative effect of the combined treatment on tumor progression is mediated through blocking both EGFR- and COX-2-related pathways. This combination regimen may provide a promising strategy for cancer therapy and chemoprevention in SCCHN.
Keimyung Author(s)(Kor)
최미선
Publisher
School of Medicine
Citation
Xin Zhang et al. (2005). Tumor Growth Inhibition by Simultaneously Blocking Epidermal Growth Factor Receptor and Cyclooxygenase-2 in a Xenograft Model. Clinical Cancer Research, 11(17), 6261–6269. doi: 10.1158/1078-0432.CCR-04-2102
Type
Article
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-04-2102
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35481
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
공개 및 라이선스
  • 공개 구분공개
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.