Src is a nonreceptor tyrosine kinase involved in the cross-talk and mediation of 
many signaling pathways that promote cell proliferation, adhesion, invasion, 
migration, and tumorigenesis. Increased Src activity has been reported in many 
types of human cancer, including gastric cancer. Therefore, this factor has been 
identified as a promising therapeutic target for cancer treatments, and 
targeting Src in gastric cancer is predicted to have potent effects. We 
evaluated the antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib 
(AZD0530), alone or combined with chemotherapeutic agents in gastric cancer cell 
lines and a NCI-N87 xenograft model. Among 10 gastric cancer cell lines, 
saracatinib specifically inhibited the growth and migration/invasion of SNU216 
and NCI-N87 cells. Saracatinib blocked the Src/FAK, HER family, and oncogenic 
signaling pathways, and it induced G(1) arrest and apoptosis in SNU216 and 
NCI-N87 cells. Apoptosis required induction of the proapoptotic BCL2 family 
member Bim. Knockdown of Bim using siRNA decreased apoptosis induced by 
treatment with saracatinib, suggesting that Bim has an important role in 
saracatinib-induced apoptosis. Saracatinib enhanced the effects of lapatinib, an 
EGFR/HER2 dual inhibitor, in SNU216 and NCI-N87 cells. Furthermore, combined 
treatment with saracatinib and 5-fluorouracil (5-FU) or cisplatin exerted 
synergistic effects in both saracatinib-sensitive and saracatinib-resistant 
cells. Consistent with our in vitro findings, cotreatment with saracatinib and 
5-FU resulted in enhanced antitumor activity in the NCI-N87 xenografts. These 
data indicate that the inhibition of Src kinase activity by saracatinib alone or 
in combination with other agents can be a strategy to target gastric cancer.