Qu Zhao, Lin Yushan, Mok Daniel Kam-Wah, Bian Qingya, Tai William Chi-Shing, Chen Sibao
State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen, Guangdong 518057, People's Republic of China.
Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, S.A.R, People's Republic of China.
Onco Targets Ther. 2020 Jun 10;13:5363-5373. doi: 10.2147/OTT.S256833. eCollection 2020.
Triple-negative breast cancer (TNBC) is a a breast cancer subtype characterized by a lack of estrogen receptor, progesterone receptor and human epidermal growth receptor 2 and is associated with poorer prognoses when compared to other breast cancers. Thus, novel anti-cancer agents with high efficacy are urgently needed. Brevilin A (BA), a natural sesquiterpene lactone, has been reported to exhibit anti-cancer effects. However, the effects of BA on TNBC have not yet been demonstrated. In this study, we investigated the anti-TNBC effects and the underlying mechanism of BA, in vitro and in vivo.
Two TNBC cell lines and a xenograft mouse model were employed to assess the effects of BA. Cell viability was detected by MTT assay. Cell cycle status and apoptosis were evaluated by flow cytometry. Cell migration was measured by wound-healing assay. Protein expression was measured by Western blotting analysis. The in vivo anti-cancer activity of BA was assessed in orthotopic tumor xenograft mice.
BA significantly inhibited the growth of TNBC cells in a dose- and time-dependent manner via induction of cell cycle arrest at G2/M phase arrest and apoptosis. BA also inhibited tumor cell migration. BA significantly downregulated the expression of Akt, mTOR, Stat3 and their phosphorylation, and thus inhibiting the activation of the Akt/mTOR and STAT3 signaling pathways. Furthermore, oral administration of BA at 25 or 50 mg/kg leads to significant inhibition of tumor growth and proliferation in tumor xenograft model mice.
BA significantly inhibited the growth and migration of TNBC cells, and induced cell cycle arrest and apoptosis. These inhibitory effects were associated with the suppression of the Akt/mTOR and Stat3 signal pathways. Based on our findings, BA possesses a promising candidate for development as an anti-cancer therapeutic drug against TNBC.
三阴性乳腺癌（TNBC）是一种乳腺癌亚型，其特征是缺乏雌激素受体、孕激素受体和人表皮生长受体2，与其他乳腺癌相比，预后较差。因此，迫切需要高效的新型抗癌药物。短叶苏木酚A（BA）是一种天然倍半萜内酯，已报道具有抗癌作用。然而，BA对TNBC的作用尚未得到证实。在本研究中，我们在体外和体内研究了BA对TNBC的抗癌作用及其潜在机制。
采用两种TNBC细胞系和一个异种移植小鼠模型来评估BA的作用。通过MTT法检测细胞活力。通过流式细胞术评估细胞周期状态和细胞凋亡。通过伤口愈合试验测量细胞迁移。通过蛋白质印迹分析测量蛋白质表达。在原位肿瘤异种移植小鼠中评估BA的体内抗癌活性。
BA通过诱导细胞周期阻滞在G2/M期和凋亡，以剂量和时间依赖性方式显著抑制TNBC细胞的生长。BA还抑制肿瘤细胞迁移。BA显著下调Akt、mTOR、Stat3及其磷酸化的表达，从而抑制Akt/mTOR和STAT3信号通路的激活。此外，以25或50mg/kg口服BA可显著抑制肿瘤异种移植模型小鼠的肿瘤生长和增殖。
BA显著抑制TNBC细胞的生长和迁移，并诱导细胞周期阻滞和凋亡。这些抑制作用与Akt/mTOR和Stat3信号通路的抑制有关。基于我们的研究结果，BA有望开发成为一种抗TNBC的抗癌治疗药物。
