1. Treatment of WiT49 cells with NVP-AEW541 induces gene expression changes associated with cell cycle arrest and PI3K/MAPK down-regulation, and sensitizes the cells to chemotherapy.
Treatment of WiT49 cells with NVP-AEW541 induces gene expression changes associated with cell cycle arrest and PI3K/MAPK down-regulation, and sensitizes the cells to chemotherapy. (A) Heat map demonstrates expression of genes associated with cell cycle progression in WiT49 cells treated with 5× GI50 of NVP-AEW541 for 1, 6, and 24 h. Genes are colored according to global, not relative, expression values (blue, down-regulated; red, up-regulated). Top-ranking gene set enrichment analysis scores for GNF2_CCNA2 [enrichment score = −0.89, P < , false discovery rate (FDR) q < ] GNF2_CKS2 (enrichment score= −0.88, P < , FDR q < ), and GNF2_CENPF (enrichment score = −0.85, P < , FDR q < ) highlights coordinate down-regulation of genes in the expression neighborhood of these cell cycle control genes. (B) Top-ranking canonical pathways identified by Ingenuity Pathway Analysis after treatment of WiT49 cells with NVP-AEW541 were those associated with PI3K/AKT (P < ) and ERK/MAPK signaling (P < ). Pathway components are colored by their global gene expression levels (green, down-regulated; red, up-regulated). (C) Median effects analysis of combining NVP-AEW541 with chemotherapeutic agents in WiT49 cells. Highly synergistic interactions are seen for doxorubicin (combination index = 0.43) and topotecan (combination index = 0.39).
Aleksandra Bielen et al. PNAS 2012;109:20:E1267-E1276
©2012 by National Academy of Sciences