TP53 mutation is considerably common in advanced high‐grade serous ovarian cancer (HGSOC) and significantly associated with a poor prognosis. In this study, we investigated the role of Cyclin G1 (CCNG1), a target gene of wild‐type TP53 (P53wt), in HGSOC and the possible regulatory mechanism between TP53 mutant (P53mt) and CCNG1 in the progression of HGSOC. High expression level of CCNG1 was found in 61.3% of HGSOC tissues and only 18.2% in fimbriae of fallopian tubes. Additionally, overexpression of CCNG1 was significantly associated with a shorter overall survival (P < 0.0001) and progression‐free survival (P < 0.0004) in HGSOC patients. In vitro, CCNG1 promoted both tumor cell motility by inducing epithelial‐mesenchymal transition (EMT) and resistance to cisplatin (CDDP). In vivo, knockdown expression of CCNG1 inhibited cancer metastasis. Furthermore, P53mt increased the expression of CCNG1 by regulating Notch3 expression, and a positive correlation between CCNG1 and Notch3 protein expression was observed by Immunohistochemistry (IHC) (r = 0.39, P: 0.01528). In conclusion, the activation of P53mt‐Notch3‐CCNG1 pathway was responsible for tumor progression to advanced disease with correlation with worse prognosis in patients with HGSOC. These data suggest a possible molecular mechanism of disease and highlights CCNG1’s potential role as a therapeutic target in HGSOC.

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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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