Zhu Xinbing, Li Rongnian, Wang Chen, Zhou Shuo, Fan Yujia, Ma Shuang, Gao Didi, Gai Nian, Yang Jing
Department of Breast Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Department of General Surgery, Panjin Liaohe Oilfield Gem Flower Hospital, Panjin, China.
Front Oncol. 2021 Jul 16;11:661184. doi: 10.3389/fonc.2021.661184. eCollection 2021.
The survival rate of breast cancer (BC) patients remains poor, thus the identification of safe and effective new drugs is crucial to improve therapeutic outcomes and overall survival. Pinocembrin (PCB), a pharmacologically active ingredient of Pinus heartwood, Eucalyptus, Euphorbia, Populus, and Sparattosperma leucanthum, has been widely applied for the treatment of various diseases and possesses anticancer activities. In vitro assays were performed to investigate the antiproliferation and antimetastasis activities of PCB in BC cells. A tumorigenesis assay with the use of murine BC models was performed to assess the antiproliferation activities of PCB . Moreover, the molecular mechanisms underlying the anticancer activities of PCB in BC cells were explored. The results showed that the anti-inhibitory and antiproliferation activities of PCB in BC might involve cell cycle (G2/M phase) arrest and apoptosis. PCB downregulated the expression levels of proteins involved in cell cycle progression and apoptosis, including cyclinB1, Cdc2, PARP1, Bcl-2, and survivin, and upregulated protein levels of cleaved PARP1, cleaved caspase3, cleaved caspase9, and BAX. In a murine subcutaneous tumor model, PCB suppressed the growth of MCF-7 cells . Low concentrations of PCB also significantly inhibited the migration and invasion abilities of BC cells. Mechanistically, PCB administration was correlated to suppression of the PI3K/AKT signaling pathway. Inhibition of the proliferation of BC cells by PCB involved cell cycle (G2/M phase) arrest and apoptosis and . Low concentrations of PCB also significantly inhibited the migration and invasion abilities of BC cells. These findings suggest that PCB might be an effective agent for treatment of BC patients.
乳腺癌(BC)患者的生存率仍然很低,因此,识别安全有效的新药对于改善治疗效果和总体生存率至关重要。松属心材、桉属、大戟属、杨属和白花油楠属植物中的药理活性成分松属素(PCB)已被广泛应用于各种疾病的治疗,并具有抗癌活性。进行体外试验以研究PCB在BC细胞中的抗增殖和抗转移活性。利用小鼠BC模型进行肿瘤发生试验,以评估PCB的抗增殖活性。此外,还探索了PCB在BC细胞中抗癌活性的分子机制。结果表明,PCB在BC中的抗抑制和抗增殖活性可能涉及细胞周期(G2/M期)阻滞和凋亡。PCB下调了参与细胞周期进程和凋亡的蛋白质表达水平,包括细胞周期蛋白B1、细胞周期蛋白依赖性激酶2(Cdc2)、聚(ADP-核糖)聚合酶1(PARP1)、B细胞淋巴瘤-2(Bcl-2)和生存素,上调了裂解的PARP1、裂解的半胱天冬酶3、裂解的半胱天冬酶9和Bax的蛋白质水平。在小鼠皮下肿瘤模型中,PCB抑制了MCF-7细胞的生长。低浓度的PCB也显著抑制了BC细胞的迁移和侵袭能力。从机制上讲,给予PCB与抑制磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/AKT)信号通路有关。PCB对BC细胞增殖的抑制涉及细胞周期(G2/M期)阻滞和凋亡,低浓度的PCB也显著抑制了BC细胞的迁移和侵袭能力。这些发现表明,PCB可能是治疗BC患者的有效药物。