Ursolic acid isolated from Isodon excisoides induces apoptosis and inhibits invasion of GBC-SD gallbladder carcinoma cells.

Gallbladder carcinoma (GBC) is a relatively rare but terminal malignancy, and drug/chemical development is an important aspect of prevention and treatment of GBC. Ursolic acid (UA), a pentacyclic triterpenoid, has been reported to exhibit various pharmaceutical effects. In the present study, the antiproliferative and anti-invasive effects of UA and the associated mechanisms in GBC were examined. UA was isolated from Isodon excisoides. The GBC cells (GBC-SD and NOZ) were treated with UA and subjected to a Cell Counting Kit-8 assay. The GBC-SD cells were subsequently selected for an Annexin V-FITC/propidium iodide assay, Transwell chamber assay, RT² profiler polymerase chain reaction (PCR) array and western blot analysis. The results indicated that UA inhibited the proliferation and invasion and induced the apoptosis of GBC-SD cells in a dose-dependent manner. Furthermore, the PCR arrays demonstrated that there were 24 differentially expressed genes between the UA-treated and untreated groups. These differentially expressed genes suggested that UA induced the apoptosis of GBC-SD cells through activation of the cell extrinsic pathway. According to Kyoto Encyclopedia of Genes and Genomes pathway analysis of these differentially expressed genes, the suppression of nuclear factor (NF)-κB and protein kinase B (Akt) signaling pathways was further validated. In summary, UA induces the apoptosis and inhibits the invasion of GBC-SD cells, which may be associated with the suppression of NF-κB and Akt signaling pathways. These results may offer a potential therapeutic strategy for the chemoprevention or chemotherapy of GBC in humans.