Regular use of aspirin after diagnosis was associated with longer survival among patients with mutated-PIK3CA colorectal cancer,but not among patients with PIK3CA wild-type cancer.In this study,we showed that combination treatment with clinically achievable concentrations of aspirin and ABT-737 could induce a synergistic growth arrest and apoptosis in several human PIK3CA wild-type cancer cells.In addition, we found that the combination of aspirin and ABT-737 resulted in a blockade of the PI3K signaling pathway.Furthermore,our data showed increased autophagy correlated with the resistance to aspirin or ABT-737 as single-agents,the enhanced autophagy induced by aspirin plus ABT-737 switched from a cytoprotective signal to a death-promoting signal.We hope that this synergy may contribute to failure of aspirin cancer therapy and ultimately lead to efficacious regimens for cancer therapy.