Targeting CHEK1: Ginsenosides-Rh2 and Cu2O@G-Rh2 nanoparticles in thyroid cancer.

IF 5.3 2区 医学 Q2 CELL BIOLOGY Cell Biology and Toxicology Pub Date : 2025-01-14 DOI:10.1007/s10565-024-09961-7
Lidong Wang, Xin Wu, XinLu Wang, Meng Dong, Hao Zhang, Pengfei Zhao
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Abstract

Thyroid cancer (THCA) is an increasingly common malignant tumor of the endocrine system, with its incidence rising steadily in recent years. For patients who experience recurrence or metastasis, treatment options are relatively limited, and the prognosis is poor. Therefore, exploring new therapeutic strategies has become particularly urgent. This study confirmed that effective suppression of THCA cell proliferation and stimulation of apoptosis can be achieved through the application of Ginsenosides-Rh2. Through network pharmacology screening, the molecular target of Ginsenosides-Rh2 in THCA was identified as CHEK1, and its inhibitory effect was confirmed by downregulating CHEK1 protein expression. Furthermore, demonstrations conducted both in vitro and in vivo showcased that delivering Ginsenosides-Rh2 using nanoparticle carriers significantly reduced cell viability by approximately 50%, regulated DNA damage levels, apoptosis-related protein expression, and cell cycle control. The IC50 of the nanoparticle formulation was determined (B-CPAP IC50 = 88.24 μM), TPC IC50 = 79.52 μM). This study confirmed that Cu2O@G-Rh2 is effective in suppressing tumors and exhibits a significant inhibitory effect on tumor recurrence and metastasis while maintaining good safety. Cu2O@G-Rh2 nanoparticles possess excellent stability and anti-tumor efficacy. This research offers new perspectives for the treatment of THCA and demonstrates potential clinical applications.

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靶向CHEK1:人参皂苷- rh2和Cu2O@G-Rh2纳米颗粒在甲状腺癌中的作用。
甲状腺癌(THCA)是一种越来越常见的内分泌系统恶性肿瘤,近年来发病率稳步上升。对于复发或转移的患者,治疗选择相对有限,预后较差。因此,探索新的治疗策略变得尤为迫切。本研究证实,人参皂苷- rh2可有效抑制THCA细胞增殖,刺激细胞凋亡。通过网络药理学筛选,确定人参皂苷- rh2在THCA中的分子靶点为CHEK1,并通过下调CHEK1蛋白表达证实其抑制作用。此外,体外和体内的实验表明,使用纳米颗粒载体递送人参皂苷- rh2可显著降低约50%的细胞活力,调节DNA损伤水平、凋亡相关蛋白表达和细胞周期控制。测定纳米颗粒配方的IC50 (B-CPAP IC50 = 88.24 μM), TPC IC50 = 79.52 μM)。本研究证实Cu2O@G-Rh2具有有效的肿瘤抑制作用,在保持良好安全性的同时,对肿瘤复发和转移具有显著的抑制作用。Cu2O@G-Rh2纳米颗粒具有优异的稳定性和抗肿瘤功效。本研究为THCA的治疗提供了新的视角,并展示了潜在的临床应用前景。
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来源期刊
Cell Biology and Toxicology
Cell Biology and Toxicology 生物-毒理学
CiteScore
9.90
自引率
4.90%
发文量
101
审稿时长
>12 weeks
期刊介绍: Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.
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