Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 7, 2006; 12(5): 703-708
Published online Feb 7, 2006. doi: 10.3748/wjg.v12.i5.703
STI571 (Glivec) suppresses the expression of vascular endothelial growth factor in the gastrointestinal stromal tumor cell line, GIST-T1
Toufeng Jin, Hajime Nakatani, Takahiro Taguchi, Takumi Nakano, Takehiro Okabayashi, Takeki Sugimoto, Michiya Kobayashi, Keijiro Araki
Toufeng Jin, Department of Tumor Surgery, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan and Department of General Surgery, College of Medical, Yanbian University, 119 Juzijie, Yanji, Jilin Province, China
Hajime Nakatani, Takumi Nakano, Takehiro Okabayashi, Takeki Sugimoto, Michiya Kobayashi, Keijiro Araki, Department of Tumor Surgery, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan
Takahiro Taguchi, Department of Human Health and Medical Science, Graduate school of Kuroshio Science, Kochi University, Nankoku, Kochi 783-8503, Japan
Correspondence to: Hajime Nakatani, MD, PhD, Department of Tumor Surgery, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan. nakatanh@med.kochi-u.ac.jp
Telephone: +81-88-880-2370 Fax: +81-88-880-2371
Received: August 9, 2005
Revised: August 9, 2005
Accepted: August 26, 2005
Published online: February 7, 2006
Abstract

AIM: To estimate whether STI571 inhibits the expression of vascular endothelial growth factor (VEGF) in the gastrointestinal stromal tumor (GIST) cells.

METHODS: We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor (SCF). Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by MTT assay.

RESULTS: Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by STI571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by MTT assay.

CONCLUSION: Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by STI571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth. but also the suppression of VEGF expression.

Keywords: c-KIT; Vascular endothelial growth factor (VEGF); STI571; Gastrointestinal stromal tumor; GIST-T1