Glioma-associated oncogene homolog 1 (GLI1) is an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human[3].GANT58 (NSC75503) has been shown to inhibit transcriptional activation by GLI1 (as well as by the other GLI species). GANT58 has been shown to inhibit GLI transactivation[4].GANT 58 (NSC 75503) is a potent GLI antagonist that inhibits GLI1-induced transcription with IC50 of 5 μM. Nude mice are treated with every second-day s.c. injections at a concentration of 50 mg/kg of cyclopamine, GANT61, GANT58, or solvent only (n=4-5 for each group). Although mice treated with these compounds showed no such signs of toxicity, this protocol is also introduced for the GANTs to be able to compare all compounds. All injections are done 2-3 cm away from the tumors. Suppression of tumor cell growth is observed for all compounds, during an 18-day treatment period. Treatment with cyclopamine or GANT58 results in the inhibition of additional xenograft growth and limited the increase in tumor size[5].GANT-58 at 5μM significantly abolished oxytocin-induced mRNA and protein expression of HIF-1α, while the nuclear abundance of Gli1 was significantly reduced by atosiban at 10μM, but was increased by oxytocin at 0.1μM in human umbilical vein endothelial cells(HUVECs). GANT-58 at 5μM also significantly abolished oxytocin-enhanced angiogenic properties of HUVECs[6].
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