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


CONCLUSIONS
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.
Jin
Toufeng
T
Department of Tumor Surgery, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.
Nakatani
Hajime
H
Taguchi
Takahiro
T
Nakano
Takumi
T
Okabayashi
Takehiro
T
Sugimoto
Takeki
T
Kobayashi
Michiya
M
Araki
Keijiro
K
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D001549:Benzamides; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D000068877:Imatinib Mesylate; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D000970:Antineoplastic Agents; D001549:Benzamides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010879:Piperazines; D011743:Pyrimidines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068877:Imatinib Mesylate; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit