Bufalin enhances the antitumor effect of gemcitabine in pancreatic cancer.

Bufalin, an active component of the Chinese medicine chan'su, has been reported to have an inhibitory effect on the growth of various types of cancer cells. In the present study, we investigated whether gemcitabine combined with bufalin enhanced the antitumor efficacy in pancreatic cancer. Three pancreatic cancer cell lines (Bxpc-3, Mia PaCa-2 and Panc-1) were treated with gemcitabine and/or bufalin in vitro. The combination treatment demonstrated greater inhibition of cellular growth and apoptosis. The activity of apoptosis signal-regulating kinase 1 (ASK1)/JNK was upregulated in gemcitabine-induced apoptosis when combined with bufalin. We also observed that tumor growth was significantly inhibited by the combination therapy in a tumor-bearing mouse model, and upregulation of ASK1 activity was validated by immunohistochemical staining. These results suggest that bufalin may be a potential chemotherapeutic agent for pancreatic cancer, which could enhance the antitumor efficacy of gemcitabine when used in combination, possibly through the activation of ASK1/JNK.