Comprehensive network pharmacology and experimentation to unveil the therapeutic efficacy and mechanisms of gypenoside LI in anaplastic thyroid cancer.

IF 3.4 2区医学 Q2 ONCOLOGY

BMC Cancer Pub Date : 2025-05-14 DOI:10.1186/s12885-025-14231-8

Meiyu Liu, Haidong Liao, Qin Peng, Junwei Huang, Weixiang Liu, Mengqiao Dai, Zanbing Li, Yang Xie, Jiafeng Liu, Yong Ying, Xiangtai Zeng

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引用次数: 0

Abstract

Background: Anaplastic thyroid cancer (ATC) is a markedly invasive subtype of thyroid cancer with a poor prognosis. The Gynostemma pentaphyllum-derived Gypenoside LI (Gyp LI) can inhibit the growth and metastasis of various tumors. This study was designed to evaluate the pharmacological mechanisms of Gyp LI against ATC via network pharmacology analysis combined with experimental verification.

Methods: Core targets and signaling pathways were obtained by using the network pharmacological analysis method. Utilizing a combination of in vitro and in vivo methodologies, we conducted a rigorous examination to ascertain the suppressive impact of Gyp LI on the ATC cell lines, specifically 8305 C and C643. Then used western blotting and immunohistochemistry to analyze the inhibitory effects of Gyp LI on SRC kinase and its downstream signaling pathways.

Results: Through integrative analysis of Gyp LI and ATC-target interactions, 78 candidate targets were identified. Network-based protein-protein interaction (PPI) analysis, combined with molecular docking, pinpointed HSP90AA1, SRC, and CASP3 as pivotal hub genes modulated by Gyp LI. KEGG enrichment analysis further emphasized the PI3K/AKT pathway, highlighting its critical involvement in ATC therapy. Gyp LI significantly inhibits ATC cell proliferation, migration, and invasion while inducing apoptosis, likely via modulation of the SRC/PI3K/AKT axis. Moreover, it enhances iodine uptake in ATC cells by regulating the sodium-iodide symporter pathway.

Conclusions: Gyp LI effectively inhibits ATC progression by modulating SRC/PI3K/AKT signaling, enhancing apoptosis, and promoting iodine uptake, offering potential therapeutic benefits for ATC treatment.

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综合网络药理学和实验揭示绞股蓝皂苷LI治疗间变性甲状腺癌的疗效和机制。

背景：间变性甲状腺癌（ATC）是一种具有明显侵袭性的甲状腺癌亚型，预后较差。绞股蓝衍生绞股蓝苷LI （Gynostemma pentaphyllum-derived Gypenoside LI, Gyp LI）具有抑制多种肿瘤生长和转移的作用。本研究旨在通过网络药理学分析结合实验验证，评价Gyp LI抗ATC的药理机制。方法：采用网络药理分析方法获得核心靶点和信号通路。利用体外和体内相结合的方法，我们进行了严格的检查，以确定Gyp LI对ATC细胞系，特别是8305c和C643的抑制作用。然后采用western blotting和免疫组化分析Gyp LI对SRC激酶及其下游信号通路的抑制作用。结果：通过对Gyp LI和atc靶点相互作用的综合分析，鉴定出78个候选靶点。基于网络的蛋白蛋白相互作用（PPI）分析，结合分子对接，确定HSP90AA1， SRC和CASP3是由Gyp LI调节的关键枢纽基因。KEGG富集分析进一步强调了PI3K/AKT通路，强调了其在ATC治疗中的关键作用。Gyp LI明显抑制ATC细胞的增殖、迁移和侵袭，同时诱导凋亡，可能是通过调节SRC/PI3K/AKT轴。此外，它通过调节碘化钠同调体途径增强ATC细胞对碘的摄取。结论：Gyp LI通过调节SRC/PI3K/AKT信号，增强细胞凋亡，促进碘摄取，有效抑制ATC进展，为ATC治疗提供潜在的治疗益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Cancer 医学-肿瘤学

CiteScore

6.00

自引率

2.60%

发文量

1204

审稿时长

6.8 months

期刊介绍： BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.