Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4

摘要: Neuroblastoma is the most common extracranial solid childhood tumor. Despite availability of advanced multimodal therapy, high-risk patients still have low survival rates. p21-activated kinase 4 (PAK4) has been shown to regulate many cellular processes in cancer cells, including migration, polarization and proliferation. However, role PAK4 neuroblastoma remains unclear. In present study, we demonstrated that was overexpressed tissues correlated with tumor malignance prognosis. To investigate function neuroblastoma, used a small-molecule inhibitor targets PAK4, is, PF-3758309. Our results showed PF-3758309 significantly induced cell cycle arrest at G1 phase apoptosis lines. Meanwhile, inhibition by increased expression CDKN1A, BAD BAK1 decreased Bcl-2 Bax. addition, screened target genes PCR array found 23 were upregulated (including TP53I3, TBX3, EEF1A2, IFNB1 MAPK8IP2) 20 downregulated TNFSF8, Bcl2-A1, Bcl2L1, SOCS3, BIRC3 NFKB1) after Moreover, via ERK signaling pathway. conclusion, study demonstrated, for first time, neuroblastomas inhibitory effect PF-3758309, which deserves further investigation as an alternative strategy treatment.