Abstract
In this study, we aimed to analyze the anti-cancer effects of β-elemene combined with paclitaxel for ovarian cancer. RT-qPCR, MTT assay, western blot, flow cytometry, and immunohistochemistry were used to analyze in vitro and in vivo anti-cancer effects of combined treatment of β-elemene and paclitaxel. The in vitro results showed that β-elemene+paclitaxel treatment markedly inhibited ovarian cancer cell growth, migration, and invasion compared to either paclitaxel or β-elemene treatment alone. Results demonstrated that β-elemene+paclitaxel induced apoptosis of SKOV3 cells, down-regulated anti-apoptotic Bcl-2 and Bcl-xl gene expression and up-regulated pro-apoptotic P53 and Apaf1 gene expression in SKOV3 cells. Administration of β-elemene+paclitaxel arrested SKOV3 cell cycle at S phase and down-regulated CDK1, cyclin-B1, and P27 gene expression and apoptotic-related resistant gene expression of MDR1, LRP, and TS in SKOV3 cells. In vivo experiments showed that treatment with β-elemene+paclitaxel significantly inhibited ovarian tumor growth and prolonged the overall survival of SKOV3-bearing mice. In addition, the treatment inhibited phosphorylated STAT3 and NF-κB expression in vitro and in vivo. Furthermore, it inhibited migration and invasion through down-regulation of the STAT-NF-κB signaling pathway in SKOV3 cells. In conclusion, the data suggested that β-elemene+paclitaxel can inhibit ovarian cancer growth via down-regulation of the STAT3-NF-κB signaling pathway, which may be a potential therapeutic strategy for ovarian cancer therapy.
Highlights
Ovarian cancer is one of the most common gynecological tumors, which can be highly mutilating, invade the adjacent tissue, and its recurrence rate is relatively high [1,2,3]
Previous reports have found that STAT3 and NF-kB signal pathways involved in growth and invasion of ovarian cancer cells [30,31,32,33]
Evidence has shown that paclitaxel can be regarded as an efficient therapy for human ovarian cancer and the therapy of paclitaxel combined with other drugs provides a potential approach to overcome the resistance of ovarian cancer [34,35,36]
Summary
Ovarian cancer is one of the most common gynecological tumors, which can be highly mutilating, invade the adjacent tissue, and its recurrence rate is relatively high [1,2,3]. The incidence of ovarian cancer in China has drastically increased since 2010, while the mortality rate has not been improved over the past 8 years [4]. Due to a paucity of effective screening modalities, most patients are diagnosed at advanced stages [5,6,7]. The most widely adopted standard treatment regimen for advanced ovarian cancer includes surgery, target therapy, and chemotherapy [8,9,10]. Tumor metastasis and resistance to apoptosis contributes to a poor survival rate in clinical ovarian cancer patients. The antiapoptosis mechanisms of ovarian cancer remain incompletely understood
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