The First Department of Gynecology, Harbin First Hospital of Heilongjiang Province, Harbin, China.
Department of Orthopedics, Harbin First Hospital of Heilongjiang Province, Harbin, China.
Braz J Med Biol Res. 2020;53(6):e8885. doi: 10.1590/1414-431x20208885. Epub 2020 May 8.
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.
在这项研究中,我们旨在分析β-榄香烯联合紫杉醇治疗卵巢癌的抗癌作用。采用 RT-qPCR、MTT 检测、western blot、流式细胞术和免疫组化分析β-榄香烯联合紫杉醇治疗对卵巢癌细胞的体内外抗癌作用。体外结果表明,与紫杉醇或β-榄香烯单药治疗相比,β-榄香烯+紫杉醇治疗明显抑制卵巢癌细胞生长、迁移和侵袭。结果表明,β-榄香烯+紫杉醇诱导 SKOV3 细胞凋亡,下调抗凋亡 Bcl-2 和 Bcl-xl 基因表达,上调促凋亡 P53 和 Apaf1 基因表达。β-榄香烯+紫杉醇处理使 SKOV3 细胞周期阻滞在 S 期,并下调 CDK1、cyclin-B1 和 P27 基因表达以及凋亡相关耐药基因 MDR1、LRP 和 TS 在 SKOV3 细胞中的表达。体内实验表明,β-榄香烯+紫杉醇治疗明显抑制卵巢肿瘤生长,延长 SKOV3 荷瘤小鼠的总生存期。此外,该治疗在体外和体内均抑制磷酸化 STAT3 和 NF-κB 的表达。此外,它通过下调 SKOV3 细胞中的 STAT-NF-κB 信号通路抑制迁移和侵袭。总之,数据表明β-榄香烯+紫杉醇可通过下调 STAT3-NF-κB 信号通路抑制卵巢癌细胞生长,可能是卵巢癌治疗的一种潜在治疗策略。