Fig. 5: PPI inhibited the PI3K-AKT-Twist1-VE-cadherin pathway.

a Gene expression profiling microarray analysis of the effect of PPI on PLC cells. GSEA revealed that PPI treatment affected numerous cellular functions including transcription, protein binding, regulation of stem cell differentiation, and blood vessel morphogenesis. b The pathway diagram according to KEGG pathway analysis showed that PPI inhibited hypoxia or VEGF-a activating the PI3K/Akt pathway, which may be responsible for the upregulation of Twist1 and the induction of VM formation. c–f Western blot analysis of the effect of wortmannin or PPI on the PI3K-AKT-Twist1-VE-cadherin pathway of PLC cells.c PI3K inhibitor (wortmannin) or PPI-reversed EET induced by hypoxia or VEGF-a. d, e The effects of PPI were confirmed by Twist overexpression or interference. After Twist1 overexpression, VE-cadherin expression was inhibited by PPI but not by the PI3K inhibitors. The knockdown assay of Twist1 further confirmed that PPI significantly decreased the VE-cadherin level than the PI3K inhibitors (n = 3)