新型 CDK4/6 抑制剂 WXJ-8 通过细胞周期对乳腺癌发挥抗癌作用

Jing Ji, Zhen Zhang, Guanrong Li, Lingyi Zuo, JIAO-JIAO Zhou, Xiu-jun Wang, SHAO-JIE Ma, Bin Liu, JIN-QING Han, Xiao Hou
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引用次数: 0

摘要

新型 Abemaciclib 衍生物 WXJ-8 可能是一种很有前景的抗肿瘤药物,但其作用机制和临床价值还需要进一步研究验证。细胞周期调节系统在孤雌生殖和发育过程中至关重要。由于 CDK4/6-CyclinD1-Rb-E2F1 信号通路参与调节细胞周期检查点,因此被认为是乳腺癌的可能治疗靶点。因此,本研究开发并合成了一种新型高特异性 CDK4/6 抑制剂 WXJ-8。WXJ-8 对乳腺癌细胞的体外活性采用 MTT 法进行检测。主要研究对象为 MDA-MB-231 和 MCF-7 细胞。平板克隆、伤口愈合、侵袭和粘附实验表明,WXJ-8 对乳腺癌细胞具有很强的抗增殖、抗迁移、抗侵袭和抗粘附作用。蛋白质印迹显示,CDK4、CDK6、p-Rb、E2F1 和 CDK4/6-CyclinD1-Rb-E2F1 通路中的其他细胞周期因子表达明显下调,Bcl-2、Caspase-3 和裂解 Caspase-3 凋亡因子表达被激活,从而导致 MDA-MB-231 细胞周期停滞和凋亡。最后,我们的研究表明,WXJ-8可能是一种潜在的抗三阴性乳腺癌候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Novel CDK4/6 lnhibitor, WXJ-8 -Exerts Anti-effects Through Cell Cycle in Breast Cancer
The novel Abemaciclib derivative WXJ-8 may be a promising anti-tumour drug; however, its mechanism of action and clinical value need to be further verified in research. Cell cycle regulating systems are critical in parthenogenesis and progression. Because of its involvement in regulating cell cycle checkpoints, the CDK4/6-CyclinD1-Rb-E2F1 signalling pathway has been proposed as a possible therapeutic target for breast cancer. As a result, WXJ-8, a new and highly specific CDK4/6 inhibitor, was developed and synthesized in this investigation. The activity of WXJ-8 against breast cancer cells in vitro was detected by MTT method. The main subjects were MDA-MB-231 and MCF-7 cells. Plate cloning, wound healing, invasion and adhesion experiments revealed that WXJ-8 had strong anti-proliferation, migration, invasion, and adhesion effects on breast cancer cells. Protein blotting revealed significant down regulation of CDK4, CDK6, p-Rb, E2F1 and other cell cycle factors in the CDK4/6-CyclinD1-Rb-E2F1 pathway, as well as activation of Bcl-2, Caspase-3, and Cleaved Caspase-3 apoptotic factor expression, resulting in MDA-MB-231 cell cycle arrest and apoptosis. Finally, our research implies that WXJ-8 might be a potential anti-triple-negative breast cancer medication candidate.
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