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

• Published in: World journal of gastroenterology : WJG 2006-02, Vol.12 (5), p.703-708
• Main Authors: Jin, Toufeng, Nakatani, Hajime, Taguchi, Takahiro, Nakano, Takumi, Okabayashi, Takehiro, Sugimoto, Takeki, Kobayashi, Michiya, Araki, Keijiro
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Base Sequence; Basic Research; Benzamides; Cell Line, Tumor; Cell Survival - drug effects; DNA - genetics; Gastrointestinal Neoplasms - drug therapy; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - metabolism; Gastrointestinal Neoplasms - pathology; Gene Expression - drug effects; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Imatinib Mesylate; Mutation; Piperazines - therapeutic use; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Pyrimidines - therapeutic use; Vascular Endothelial Growth Factor A - genetics
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v12.i5.703

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