In vitro study | AG-1024 inhibits insulin-like growth factor -1 (IGF-1) and insulin-stimulated cell proliferation with IC50 of 0.4 μm and 0.1 μm, respectively, and inhibits IGF-1 receptor and insulin receptor autophosphorylation, IC50 of 7 μm and 57 μm, respectively, also inhibited the activity of receptor tyrosine kinase on exogenous substrate (TKA), IC50 of 18 μm and 80 μm, respectively. AG-1024 (10 μm) acts on MCF-7 cells and inhibits cell proliferation after 48 hours of treatment. This effect is time-dependent and induces cell apoptosis with an apoptosis rate of 20.1%, when combined with Irradiation (10 Gy), the apoptosis rate was more than 40%, when Irradiation (10 Gy) alone, the apoptosis rate was only 11.8, and the down-regulation of p-Akt1 and bcl-2, and Bax, upregulation of p53 and p21 correlates. In the presence of serum, AG-1024 significantly inhibits the proliferation of malignant melanoma cells by inhibiting the MAPK/ERK2 signaling pathway, followed by rapid induction of pRb dephosphorylation, and finally inhibiting the formation of the pRb-E2F complex, IC50<50 nM. AG-1024 acts on UT7-9 and Ba/F3-p210 cells, down-regulates Bcr-Abl and P-Akt expression, and up-regulates DNA-PKcs expression, resulting in decreased survival and proliferation of cloned genes. AG-1024 also significantly inhibited cell proliferation of the anti-BCR-ABL inhibitor STI571, associated with a dose-dependent decrease in Bcr-Abl protein expression. |