Potentiation of the effect of gemcitabine by emodin in pancreatic cancer is associated with survivin inhibition

Pancreatic cancer is one human malignancy which has chemoresistant behavior to gemcitabine treatment. In this study, we revealed that emodin, an active component from Chinese medicinal herbs, could enhance pancreatic cancer cells apoptosis induced by gemcitabine. Survivin, a member of the inhibitor of apoptosis gene family, is involved in control of cell division and inhibition of apoptosis and described as a beta-catenin/Tcf/Lef target gene. Western blot and PCR analysis showed that emodin suppressed survivin expression in a close- and time-dependent manner. We further demonstrated survivin expression could be up-regulated by gemcitabine. Surprisingly, survivin expression induced by gemcitabine could be inhibited in combination with emodin treatment. Moreover, cells treated with gemcitabine and emodin showed a preferential peri-plasma membrane position of beta-catenin, blocking the translocation of beta-catenin to nucleus induced by gemcitabine. In addition to these in vitro results, we also found that emodin potentiates the antitumor effects of gemcitabine in vivo by down-regulating the expression of survivin and beta-catenin. Taken together, these results suggest that emodin potentiates gemcitabine antitumor activity through suppression of survivin gene in pancreatic cancer. (c) 2009 Elsevier Inc. All rights reserved.