IM-412 inhibits the invasion of human breast carcinoma cells by blocking FGFR-mediated signaling

摘要: Triple-negative breast cancer (TNBC) is an aggressive with a poor prognosis due to its epithelial‑to-mesenchymal transition (EMT) phenotype. Cancer patients often experience several detrimental effects of treatment, such as chemoresistance, radioresistance and the maintenance stem cells EMT. Thus, EMT signaling considered be valuable therapeutic target for inhibition being attempted new treatment option TNBC patients. Previously, we showed that 3-(2-chlorobenzyl)-1,7-dimethyl-1H-imidazo[2,1-f]purine‑2,4(3H,8H)-dione (IM-412) inhibits transforming growth factor-β (TGF-β)-induced differentiation human lung fibroblasts through both Smad-dependent and -independent pathways. In present study, examined inhibitory effect IM-412 on pathways invasiveness in since TGF-β pathway typical functions not only potently suppressed migration invasion MDA-MB-231 cells, but also lowered expression mesenchymal markers EMT-activating transcription factors these cells. inhibited activation proteins, including Smad2/Smad3, p38MAPK, Akt JNK, it attenuated phosphorylation FGFR1 FGFR3. Collectively, our findings suggest synthetic compound process MDA-MB-231 cells thereby effectively could serve novel agent malignant cancers.