Songorine suppresses cell growth and metastasis in epithelial ovarian cancer via the Bcl‑2/Bax and GSK3β/β‑catenin signaling pathways

Zhang,Hongxia; Dong,Ruifeng; Zhang,Ping; Wang,Yankui

doi:10.3892/or.2019.7070

Songorine suppresses cell growth and metastasis in epithelial ovarian cancer via the Bcl‑2/Bax and GSK3β/β‑catenin signaling pathways

Authors:
- Hongxia Zhang
- Ruifeng Dong
- Ping Zhang
- Yankui Wang
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Affiliations: Department of Obstetrics, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266011, P.R. China, Department of Gynecology, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong 266011, P.R. China, Department of Obstetrics and Gynecology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: March 15, 2019 https://doi.org/10.3892/or.2019.7070
Pages: 3069-3079

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Abstract

Epithelial ovarian cancer (EOC) is the most frequent cause of cancer‑associated mortality among all types of gynecological cancer. The high recurrence rate and the poor 5‑year survival rate indicate that more effective therapeutic strategies are required. The aim of the present study was to investigate the role and potential mechanisms of songorine in treating EOC. EOC cells were cultured with different concentrations of songorine, following which MTT and flow cytometric analyses were conducted to measure cell viability and apoptosis. Wound healing and Transwell assays were used to detect cell migration and invasion abilities. Furthermore, associated molecules in the glycogen synthase kinase (GSK)‑3β/β‑catenin and B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X (Bax) signaling pathways were semi‑quantified by western blotting. Finally, tumor size measurements, pathological observations, western blot analysis and toxicological evaluations were performed in SKOV‑3 tumor‑bearing BALB/c nude mice to investigate the efficacy and safety of songorine. As expected, songorine inhibited EOC cell survival, invasion and migration, promoted EOC cell apoptosis and suppressed mammalian EOC tumorigenic behavior. In particular, GSK3β inhibitor treatment restored the songorine‑induced regulation of the GSK3β/β‑catenin signaling pathway. Furthermore, in the in vitro and in vivo experiments, songorine consistently downregulated the expression of N‑cadherin, vimentin, matrix metalloproteinase (MMP)‑2, MMP‑9, phosphorylated‑GSK3β, β‑catenin and Bcl‑2, and upregulated the expression of E‑cadherin, cleaved caspase‑3, cleaved caspase‑9 and Bax. In conclusion, songorine exerted its anticancer effect through the GSK3β/β‑catenin and Bcl‑2/Bax signaling pathways. These results highlight the potential use of songorine as a novel therapeutic agent for EOC.

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