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

Chen,Huiping; Wu,Xiujuan; Duan,Yitao; Zhi,Dexian; Zou,Min; Zhao,Zhihong; Zhang,Xiaojun; Yang,Xiaoang; Zhang,Jianying

doi:10.3892/ol.2019.10397

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

Authors:
- Huiping Chen
- Xiujuan Wu
- Yitao Duan
- Dexian Zhi
- Min Zou
- Zhihong Zhao
- Xiaojun Zhang
- Xiaoang Yang
- Jianying Zhang
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Affiliations: Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Cardiology, Zhengzhou University People's Hospital (Henan Provincial People's Hospital), Zhengzhou, Henan 450003, P.R. China, Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, P.R. China
Published online on: May 27, 2019 https://doi.org/10.3892/ol.2019.10397
Pages: 1467-1474

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Abstract

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.

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