The novel kinase inhibitor EMD1214063 is effective against neuroblastoma.

摘要: Background Children with high-risk neuroblastoma have poor survival rates, and novel therapies are needed. Previous studies identified a role for the HGF/c-Met pathway in pathogenesis. We hypothesized that EMD1214063 would be effective against tumor cells tumors preclinical models via inhibition of signaling. Methods determined expression c-Met protein by Western blots panel cell lines viability after treatment using MTT assays. TUNEL assays DNA ladder formation, were performed to measure induction apoptosis treatment. Inhibition intracellular signaling was measured blot analysis treated untreated cells. To investigate efficacy vivo, injected orthotopically into immunocompromised mice, mice oral EMD1214063. Tumors evaluated growth, histologic appearance, immunohistochemistry. Results All sensitive EMD1214063, IC50 values ranged from 2.4 8.5 μM. inhibited HGF-mediated phosphorylation MEK induced all tested lines. In xenograft tumors, reduced growth. Conclusions Treatment inhibits HGF-induced results death. is also reducing growth vivo. therefore represents therapeutic agent neuroblastoma, further warranted.