STI571 (Glivec) suppresses the expression of vascular endothelial growth factor in the gastrointestinal stromal tumor cell line,GIST-T1  

作　　者：Toufeng Jin Hajime Nakatani Takahiro Taguchi Takumi Nakano Takehiro Okabayashi Takeki Sugimoto Michiya Kobayashi Keijiro Araki 

机构地区：[1]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 [2]Department of Tumor Surgery, Kochi-Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan [3]Department of Human Health and Medical Science, Graduate school of Kuroshio Science, Kochi University,Nankoku, Kochi 783-8503, Japan

出　　处：《World Journal of Gastroenterology》2006年第5期703-708,共6页世界胃肠病学杂志（英文版）

摘　　要：AIM： To estimate whether S-TI571 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 PITT 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 S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION： Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. 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.AIM:To estimate whether STI571 inhibits the expressionof vascular endothelial growth factor(VEGF)in thegastrointestinal stromal tumor(GIST)cells.METHODS:We used GIST cell line,GIST-T1.It hasa heterogenic 57-bp deletion in exon 11 to produce amutated c-KIT,which results in constitutive activationof c-KIT.Cells were treated with/without STI571 orstem cell factor(SCF).Transcription and expression ofVEGF were determined by RT-PCR and flow cytometryor Western blotting,respectively.Activated c-KIT wasestimated by immunoprecipitation analysis.Cell viabilitywas determined by MTT assay.RESULTS:Activation of c-KIT was inhibited bySTI571 treatment.VEGF was suppressed at both thetranscriptional and translational levels in a temporal anddose-dependent manner by STI571.SCF upregulatedthe expression of VEGF and it was inhibited by STI571.STI571 also reduced the cell viability of the GIST-T1cells,as determined by MTT assay.CONCLUSION:Activation of c-KIT in the GIST-T1regulated the expression of VEGF and it was inhibited bySTI571.STI571 has antitumor effects on the GIST cellswith respect to not only the inhibition of cell growth,butalso the suppression of VEGF expression.

关 键 词：C-KIT Vascular endothelial growth factor（VEGF） S-13571 Gastrointestinal stromal tumor GIST-T1 

分 类 号：R735[医药卫生—肿瘤]