Ras-GTPase-activating protein SH3 domain-binding proteins (G3BP) are 
overexpressed in various human tumors and participate in several signaling 
pathways involved in growth, differentiation and apoptosis. G3BP interact with 
RasGAP (Ras-GTPase activating protein) only in growing cells and depend on Ras 
activation, and participate in the Ras signal pathway. Therefore, the blockage 
and downregulation of G3BP may be a new strategy for cancer therapy. In this 
report, we demonstrate that a novel peptide GAP161 blocked the functions of G3BP 
and markedly suppressed HCT116 cell growth through the induction of apoptosis. 
The peptide bound with G3BP, which interfered with the interaction of G3BP1 with 
RasGAP and further suppressed Ras signaling pathways. GAP161 downregulated G3BP1 
and G3BP2 proteins. Similarly, the knockdown of G3BP substantially decreased the 
proliferation of HCT116 cells and inhibited Ras signal pathways. Furthermore, 
the downregulation of G3BP could enhance cisplatin-induced apoptosis and growth 
inhibition of HCT116 cells. We also found that GAP161 suppressed the growth of 
BALB/c mice bearing colon CT26 tumors and nude mice bearing HCT116 xenografts. 
These results suggest that downregulation of G3BP might be useful in cancer 
therapy and that GAP161 is a promising new therapeutic agent for cancers.