SUD Raw data.zip

The transient receptor potential melastatin 7 channels (TRPM7), a non-selected cations ion channel, exhibite high expression in some human cancer tissues and involved in proliferation, migration, invasion and EMT etc. of cancer cells. As a good therapeutic target of cancer, the lack of efficient and highly selective TRPM7 modulations is a big issue. N- [ 4- (4, 6- dimethyl- 2- pyrimidinyloxy) - 3- methylphenyl] -N' - [ 2 -(dimethylamino)] benzoylurea (SUD) is a newly synthesized benzoylurea derivative. Our previous studies proved that SUD inhibited the growth through inducing cell-cycle arrest and apoptosis in MCF-7 and BGC-823 cell lines. In this study, we checked the effect of SUD on the migration of cancer cells by trans-well assay and wound-healing. The results show that SUD decrease the migration of breast cancer (MCF-7) and gastric cancer (BGC-823) cells significantly both in the conditions incubated with and without EGF. In addition, we test the expression of Epithelial mesenchymal transition (EMT)-related proteins by western blot and RT-PCR. SUD decrease the expression of vimentin and increased the expression of E-cadherin in MCF-7 and BGC-823 cells, means EMT also be decreased by SUD. TRPM7 play important roles in the migration induced by EGF as we reported. So, we tested the effect of SUD on TRPM7 current and expression through Patch clamp and qPCR. We found that SUD not only reduced the TRPM7 current amplitude through direct binding to the channel, but also decreased the expression through PI3K/Akt signaling pathway. At last, we try to predicted the binding site of SUD on TRPM7 by Molecular docking analysis, which should provide some clues for new TRPM7 inhibitor found. In summary, our research demonstrated that SUD is an effective TRPM7 inhibitor and a potential agents to suppress metastasis of breast and gastric cancer through inhibit TRPM7 expression and function.