Terrestrosin D inhibits invasion and induces apoptosis through inhibition of STAT3 in anaplastic thyroid carcinoma

IF 1.1 4区 医学 Q4 TOXICOLOGY Molecular & Cellular Toxicology Pub Date : 2024-06-03 DOI:10.1007/s13273-024-00457-3
Honglai Zhang, Dawei Sun, Peijie Lei, Jingjing Cheng
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Abstract

Background

The prognosis with current management approach of anaplastic thyroid carcinoma (ATC) remains poor, and new effective treatments are greatly needed. Terrestrosin D (TED) is active component of traditional Chinese medicine (TCM) Tribulus terrestris L. with anti-tumor and anti-inflammatory activities. However, it remains unclear about the activity and mechanisms of TED in ATC.

Objectives

In this study, the experimental groups included control, DMSO, TED (2.5 μM), and TED (5 μM). We detected cell viability, invasion, migration, and apoptosis to assess the effects of TED on ATC cells in vitro. Next, we performed western blot to determine apoptosis-related proteins and STAT3 protein expression. In addition, the possible mechanism of TED anti-cancer effects on ATC was preliminarily investigated through network pharmacology.

Results

These results showed that TED groups could significantly inhibit cell viability, invasion, migration, and colony formation ability, and promote the cell apoptosis, compared with the DMSO group. Besides, TED obviously downregulated the levels of Bcl-2, and STAT3 protein, increased level of Bax and caspase-3 protein. Network pharmacological analysis showed that 27 intersecting genes were obtained by intersecting TED and ATC target gene sets, of which STAT3 had the best correlation.

Conclusions

We found that TED has strong anti-cancer activities on ATC, which could induce cell apoptosis through the regulation of STAT3. This study provides a new idea to treat ATC.

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Terrestrosin D 通过抑制 STAT3 抑制无性甲状腺癌的侵袭并诱导其凋亡
背景甲状腺无节细胞癌(ATC)目前的治疗方法预后仍然不佳,亟需新的有效治疗方法。蒺藜素 D(TED)是传统中药蒺藜的活性成分,具有抗肿瘤和抗炎活性。本研究的实验组包括对照组、二甲基亚砜组、TED(2.5 μM)组和 TED(5 μM)组。我们检测了细胞活力、侵袭、迁移和凋亡,以评估 TED 在体外对 ATC 细胞的影响。接着,我们用 Western 印迹法检测了细胞凋亡相关蛋白和 STAT3 蛋白的表达。结果表明,与 DMSO 组相比,TED 组能显著抑制细胞活力、侵袭、迁移和集落形成能力,促进细胞凋亡。此外,TED能明显降低Bcl-2和STAT3蛋白的水平,提高Bax和caspase-3蛋白的水平。网络药理学分析表明,TED与ATC靶基因组交叉得到27个交叉基因,其中STAT3的相关性最好。这项研究为治疗 ATC 提供了新思路。
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来源期刊
CiteScore
2.50
自引率
17.60%
发文量
114
审稿时长
6-12 weeks
期刊介绍: Molecular & Cellular Toxicology publishes original research and reviews in all areas of the complex interaction between the cell´s genome (the sum of all genes within the chromosome), chemicals in the environment, and disease. Acceptable manuscripts are the ones that deal with some topics of environmental contaminants, including those that lie in the domains of analytical chemistry, biochemistry, pharmacology and toxicology with the aspects of molecular and cellular levels. Emphasis will be placed on toxic effects observed at relevant genomics and proteomics, which have direct impact on drug development, environment health, food safety, preventive medicine, and forensic medicine. The journal is committed to rapid peer review to ensure the publication of highest quality original research and timely news and review articles.
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