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重楼皂苷Ⅲ通过GSK-3β/β-连环蛋白通路调控肺癌细胞的上皮-间质转化。

Polyphyllin Ⅲ regulates EMT of lung cancer cells through GSK-3β/β-catenin pathway.

作者信息

Liu Qian, Luo Zhuang, Yang Jiao

机构信息

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.

出版信息

Ann Med Surg (Lond). 2024 Jan 15;86(3):1376-1385. doi: 10.1097/MS9.0000000000001629. eCollection 2024 Mar.

Abstract

BACKGROUND

Some studies have found that the application of traditional Chinese medicine in the treatment of lung cancer has achieved satisfying results. Polyphyllin Ⅲ (PP Ⅲ) is a natural steroid saponin from P. polyphylla var. yunnanensis, and its analogs have played a wide role in anticancer research. This study aimed to investigate the effect of PP Ⅲ on the development of lung cancer and its molecular mechanism.

METHODS

A549 and NCI-H1299 cell lines were treated with PP Ⅲ in gradient concentration to detect the IC50 of the cells, and the optimal concentration was selected for subsequent experiments. The effects of PP III treatment on lung cancer were investigated in vitro and in vivo.

RESULTS

In vitro experiments, it was found that the proliferation, invasion, migration, and colony formation ability of cancer cells were significantly reduced after PP III treatment, while accompanied by a large number of cell apoptosis. Further detection showed that N-cadherin was significantly decreased, E-cadherin was increased, and Snail and Twist were decreased in A549 cells and NCI-H1299 cells, respectively. In addition, GSK-3β expression was increased, while β-catenin expression was reduced with PP III treatment. In the mouse model, it was demonstrated that the volume of transplanted tumors was significantly reduced after PP Ⅲ treatment.

CONCLUSIONS

PP Ⅲ has the capacity to inhibit the progression of lung cancer and regulate epithelial-mesenchymal transition through the GSK-3β/β-catenin pathway to suppress the malignant behavior of cancer cells. The application of PP Ⅲ is expected to be an effective method for the treatment of lung cancer.

摘要

背景

一些研究发现,中药在肺癌治疗中取得了令人满意的效果。重楼皂苷Ⅲ(PPⅢ)是云南重楼中的一种天然甾体皂苷,其类似物在抗癌研究中发挥了广泛作用。本研究旨在探讨PPⅢ对肺癌发展的影响及其分子机制。

方法

用不同浓度的PPⅢ处理A549和NCI-H1299细胞系,检测细胞的半数抑制浓度(IC50),并选择最佳浓度用于后续实验。在体外和体内研究PPⅢ处理对肺癌的影响。

结果

体外实验发现,PPⅢ处理后癌细胞的增殖、侵袭、迁移和集落形成能力显著降低,同时伴有大量细胞凋亡。进一步检测显示,A549细胞和NCI-H1299细胞中,N-钙黏蛋白显著降低,E-钙黏蛋白增加,Snail和Twist分别降低。此外,PPⅢ处理后糖原合成酶激酶-3β(GSK-3β)表达增加,而β-连环蛋白表达降低。在小鼠模型中,证明PPⅢ处理后移植瘤体积显著减小。

结论

PPⅢ具有抑制肺癌进展的能力,并通过GSK-3β/β-连环蛋白途径调节上皮-间质转化,以抑制癌细胞的恶性行为。PPⅢ的应用有望成为治疗肺癌的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b9/10923388/9b4ded8fc6c1/ms9-86-1376-g001.jpg

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