Niu Junjie, Hu Jinyang, Wang Zhu
Department of Medical Oncology, Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, No. 58, Lushan Road, Yuelu District, Changsha, Hunan Province 410000, P. R. China.
Toxicol Res (Camb). 2024 Mar 21;13(2):tfae033. doi: 10.1093/toxres/tfae033. eCollection 2024 Apr.
Triple-negative breast cancer (TNBC) lacks effective therapeutic targets. Scutellaria barbata D.Don (SB) has been revealed to have anti-breast cancer (BC) effect, but the effect of SB extract in TNBC is still unclear. Herein, this research delves into the underlying mechanism.
SB was extracted by solvent extraction, and the main components were identified using an Agilent 6,520 HPLC-Chip/Q-TOF (Chip/Q-TOF) MS system. In vitro cell experiments were conducted. The effects of SB extract alone, SB extract plus EGF, GSK alone, GSK plus Ezrin overexpression, or SB extract plus Ezrin overexpression on cell viability, invasion, migration, and apoptosis were examined by cell function experiments. The apoptosis- and RhoA/ROCK1 pathway-related protein levels were analyzed by western blot assay.
Mass spectrometry analysis exhibited that SB extract mainly contains long-chain fatty acids and ursolic acid. SB extract mitigated TNBC cell biological phenotypes, apoptosis- and RhoA/ROCK1 pathway-related marker expressions, which were reversed by EGF. The further results found that GSK obviously weakens TNBC cell biological behaviors, apoptosis- and RhoA/ROCK1 signaling-related protein levels, while oe-Ezrin treatment reverses the effect of GSK on TNBC cells. Moreover, SB extract regulated Ezrin-mediated function of TNBC cells by impeding the RhoA/ROCK1 pathway.
Our findings demonstrated that SB extract regulated Ezrin-mediated proliferation, migration, invasion, and apoptosis of TNBC cells via suppressing the RhoA /ROCK1 signaling. Our results offer the experimental foundation for further investigation of the anti-cancer role of SB in TNBC cells.
SB extract inhibits the biological phenotypes of TNBC cells.SB extract inhibits the biological behaviors of TNBC cells through the RhoA/ROCK1 pathway.SB extract modulates Ezrin-mediated TNBC cell proliferation, migration, invasion, and apoptosis via restraining the RhoA/ROCK1 signaling.
三阴性乳腺癌（TNBC）缺乏有效的治疗靶点。半枝莲已被证实具有抗乳腺癌作用，但半枝莲提取物对TNBC的作用仍不清楚。在此，本研究深入探讨其潜在机制。
采用溶剂萃取法提取半枝莲，利用安捷伦6520高效液相色谱-芯片/四极杆飞行时间质谱（Chip/Q-TOF）系统鉴定主要成分。进行体外细胞实验。通过细胞功能实验检测单独使用半枝莲提取物、半枝莲提取物加表皮生长因子（EGF）、单独使用糖原合成酶激酶（GSK）、GSK加埃兹蛋白过表达，或半枝莲提取物加埃兹蛋白过表达对细胞活力、侵袭、迁移和凋亡的影响。通过蛋白质印迹法分析凋亡及RhoA/ROCK1通路相关蛋白水平。
质谱分析显示，半枝莲提取物主要含有长链脂肪酸和熊果酸。半枝莲提取物减轻了TNBC细胞的生物学表型、凋亡及RhoA/ROCK1通路相关标志物表达，而EGF可逆转这些作用。进一步结果发现，GSK明显削弱TNBC细胞的生物学行为、凋亡及RhoA/ROCK1信号相关蛋白水平，但埃兹蛋白过表达处理可逆转GSK对TNBC细胞的作用。此外，半枝莲提取物通过抑制RhoA/ROCK1通路调节埃兹蛋白介导的TNBC细胞功能。
我们的研究结果表明，半枝莲提取物通过抑制RhoA/ROCK1信号通路调节埃兹蛋白介导的TNBC细胞增殖、迁移、侵袭和凋亡。我们的结果为进一步研究半枝莲在TNBC细胞中的抗癌作用提供了实验基础。
半枝莲提取物抑制TNBC细胞的生物学表型。半枝莲提取物通过RhoA/ROCK1通路抑制TNBC细胞的生物学行为。半枝莲提取物通过抑制RhoA/ROCK1信号调节埃兹蛋白介导的TNBC细胞增殖、迁移、侵袭和凋亡。
