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靶向CHEK1:人参皂苷-Rh2与Cu2O@G-Rh2纳米颗粒在甲状腺癌中的应用

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

作者信息

Wang Lidong, Wu Xin, Wang XinLu, Dong Meng, Zhang Hao, Zhao Pengfei

机构信息

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.

Department of Ultrasound, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, People's Republic of China.

出版信息

Cell Biol Toxicol. 2025 Jan 14;41(1):30. doi: 10.1007/s10565-024-09961-7.

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.

摘要

甲状腺癌(THCA)是一种日益常见的内分泌系统恶性肿瘤,近年来其发病率呈稳步上升趋势。对于出现复发或转移的患者,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,通过应用人参皂苷-Rh2可有效抑制THCA细胞增殖并诱导细胞凋亡。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蛋白表达证实了其抑制作用。此外,体外和体内实验均表明,使用纳米颗粒载体递送人参皂苷-Rh2可使细胞活力显著降低约50%,调节DNA损伤水平、凋亡相关蛋白表达和细胞周期调控。测定了纳米颗粒制剂的IC50(B-CPAP细胞系的IC50 = 88.24 μM,TPC细胞系的IC50 = 79.52 μM)。本研究证实,Cu2O@G-Rh2在抑制肿瘤方面有效,对肿瘤复发和转移具有显著抑制作用,同时保持良好的安全性。Cu2O@G-Rh2纳米颗粒具有优异的稳定性和抗肿瘤疗效。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价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e1/11732901/09d353fcbc37/10565_2024_9961_Fig1_HTML.jpg

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