Inhibition of Src reduces gemcitabine-induced cytotoxicity in human pancreatic cancer cell lines

In the present study, we examined the role of Src in gemcitabine-induced cell growth suppression in human pancreatic cancer cell lines. In two human pancreatic cancer cell lines, PK-9 and MIA PaCa-2, we found that a selective Src protein tyrosine kinase inhibitor, PP2, inhibited gemcitabine-induced cell growth suppression. When dominant negative src cDNA was constitutively expressed in PK-9 cells (PK-9-Src-DN), the degree of gemcitabine-induced cell growth suppression was decreased compared with that of mock-transfected PK-9 cells. The mechanism of the inhibitory effect of gemcitabine-induced cytotoxicity was found to be the suppression of apoptosis, which was downregulated in PK-9-Src-DN cells. These results indicate that Src mediates signals that culminate in suppressing cell growth and survival in the presence of gemcitabine, at least in particular cell lines.