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中药配方通过恢复视网膜母细胞瘤蛋白功能和抑制极光激酶活性诱导细胞周期停滞和凋亡。

The Traditional Chinese Medicine Formula Induces Cell Cycle Arrest and Apoptosis through Restoration of Retinoblastoma Protein Function and Inhibition of Aurora Kinase Activity.

作者信息

Chang Chih-Jui, Wu Cheng-Chia, Hsieh Yi-Jen, Chen Jhong-Kuei, Kung Yen-Lun, Tsai Wan-Ting, Huang Hsuan-Shun, Lin Shinn-Zong, Ho Tsung-Jung

机构信息

Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan.

Department of Chinese Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan.

出版信息

J Cancer. 2025 Jul 11;16(10):3180-3191. doi: 10.7150/jca.114495. eCollection 2025.

Abstract

Traditional Chinese Medicine (TCM) has a long-standing history in treating various diseases, including cancer. Wu Bao San is a traditional formula known for its ability to clear heat, detoxify, relieve cough and phlegm and treat tumours. The modified Wu Bao San (MWBS) is a conventional medicine prescribed by doctors of Chinese medicine. However, the molecular mechanisms underlying the anticancer effects remain unclear owing to the complexity of the components of traditional Chinese medicine, making it challenging to pinpoint specific molecular targets or pathways underlying their clinical effect. In this study, we used an MTT assay, flow cytometry, indirect immunofluoresence imaging, and western blotting to analyse the viability, cell cycle profiles, morphology, and protein levels of cells after MWBSE treatment. Our results showed that MWBSE has multiple anticancer effects. First, MWBSE induces cytokinesis failure by inhibiting Aurora kinase, leading cells to commit to cell death. Additionally, MWBSE reduces the phosphorylation of Rb, restoring its function and resulting in cell cycle arrest. The overexpression of Aurora kinases plays a pivotal role in sustaining malignant cell behaviors such as uncontrolled growth, colony formation, and tumor development. The retinoblastoma protein (Rb) is a key tumor suppressor that regulates the cell cycle, particularly the transition from the G1 to the S phase due to its significant involvement in tumor biology. Aurora kinases and Rb have emerged as promising targets for cancer therapy. Our findings provide a mechanistic explanation of the targets and anti-tumor pathways of MWBSE.

摘要

中医在治疗包括癌症在内的各种疾病方面有着悠久的历史。五宝散是一种传统方剂,以清热、解毒、止咳化痰及治疗肿瘤的能力而闻名。改良五宝散(MWBS)是中医医生开具的一种传统药物。然而,由于中药成分的复杂性,其抗癌作用的分子机制仍不清楚,这使得确定其临床效果背后的特定分子靶点或途径具有挑战性。在本研究中,我们使用MTT法、流式细胞术、间接免疫荧光成像和蛋白质印迹法来分析MWBSE处理后细胞的活力、细胞周期分布、形态和蛋白质水平。我们的结果表明,MWBSE具有多种抗癌作用。首先,MWBSE通过抑制极光激酶诱导胞质分裂失败,导致细胞走向死亡。此外,MWBSE降低Rb的磷酸化,恢复其功能并导致细胞周期停滞。极光激酶的过表达在维持恶性细胞行为如不受控制的生长、集落形成和肿瘤发展中起关键作用。视网膜母细胞瘤蛋白(Rb)是一种关键的肿瘤抑制因子,它调节细胞周期,特别是从G1期到S期的转变,因为它在肿瘤生物学中具有重要作用。极光激酶和Rb已成为有前景的癌症治疗靶点。我们的研究结果为MWBSE的靶点和抗肿瘤途径提供了机制解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0216/12305626/34cdf239d9fd/jcav16p3180g001.jpg

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