Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells

Abstract

The antitumor activity of oleanolic (OA) has attracted attention due to its marked antitumor effects and pharmacological safety. In the present study, the effects of the combination of OA and 5-fluorouracil (5-FU) on Panc-28 human pancreatic cells were studied. The results showed that combined use of OA and 5-FU synergistically potentiated cell death effects on Panc-28 cells, and the pro-apoptotic effects were also increased. Further study revealed that the combined treatment could enhance mitochondrial depolarization, lysosomal membrane permeabilization (LMP) and leakage of cathepin D, while the release of cytochrome C did not display significant changes. The expression of apoptosis related proteins was also affected in cells treated with the combination of OA and 5-FU, including activation of caspases-3 and the expression of Bcl-2/Bax, survivin and NF-κB. Our results provide evidence that combination of OA and 5-FU may serve as a novel strategy for the treatment of pancreatic cancer.