Ursolic acid synergistically enhances gemcitabine-induced apoptosis in bladder cancer via the PI3K/AKT and JNK signaling pathways

Ursolic acid (UA) is a natural compound that exists in a number of Chinese medicinal herbs, which has been demonstrated to enhance the efficacy of chemotherapy in multiple types of cancer. The present study aimed to observe whether UA enhances the antitumor effects of gemcitabine (GEM) in human bladder cancer (BCa) cell lines, and to investigate the possible underlying mechanisms. The human BCa cell lines, T24 and 5637, were treated with GEM and/or UA in vitro. Cell viability was measured by the Cell Counting Kit-8 assay. Apoptosis was detected using Hoechst 33258 staining, western blot analysis and flow cytometry. The expression levels of signaling pathway-related proteins were detected using western blot analysis. UA and GEM synergistically inhibited the proliferation of human BCa cells. Compared with GEM treatment alone, the combination of GEM and UA led to enhanced the antitumor effects, which were associated with the induction of apoptosis. The PI3K/AKT and JNK signaling pathways were involved in human BCa cells treated with GEM and UA. Both the AKT activator, SC79, and the JNK inhibitor, SP600125, reduced the expression of cleaved PARP and cleaved caspase-3. On the whole, the results of the present study demonstrate that UA enhances GEM-induced apoptosis by inactivating the PI3K/AKT signaling pathway and activating the JNK signaling pathway in human BCa cells.