Atractylodin induces apoptosis through downregulation of PI3Kγ-mediated PI3K/Akt/mTOR/p70S6K signalling in colon cancer cells and suppresses the tumour formation in xenograft mice model

IF 2.8 4区工程技术 Q2 POLYMER SCIENCE Macromolecular Research Pub Date : 2023-11-28 DOI:10.1007/s13233-023-00220-y

Wenyi Lu, Jianxia Liu, Bin Wu, Shungen Huang, Jian Wang, Runda Wu, Zhongqi Mao

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Abstract

This study used both in vitro and in vivo models to evaluate the efficacy of atractylodin as an anticancer treatment for colorectal cancer. The cytotoxicity of atractylodin on colon cancer cells was assessed using the MTT assay, and atractylodin-induced apoptosis was determined using flow cytometry. The expression of cleaved caspase 3 and other apoptotic proteins was examined using Western blotting to determine the mechanism underlying atractylodin's anticancer activity. In addition, the role of PI3K/Akt/mTOR/p70S6K signalling in atractylodin-induced apoptosis in colon cancer cells was analyzed. The study found that atractylodin caused dose-dependent ROS-mediated apoptosis and DNA damage in colon cancer cells and activated caspase 3. Furthermore, atractylodin inhibited the PI3K/Akt/mTOR/p70S6K signalling pathway by targeting PI3Kγ in colon cancer cells. Molecular docking analysis indicated that atractylodin binds to the Akt binding pocket of PI3Kγ. The study also evaluated the antitumour effects of atractylodin on a colon cancer tumour xenograft model and found that it significantly reduced tumour growth and volume by inducing apoptosis. These results suggest that atractylodin has potential as a candidate for the treatment of colorectal cancer, although further research is necessary.

Graphical abstract

Atractylodin induces apoptosis in colon cancer cells.

Abstract Image

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在异种移植小鼠模型中，苍术素通过下调PI3Kγ介导的PI3K/Akt/mTOR/p70S6K信号通路诱导结肠癌细胞凋亡，抑制肿瘤形成

本研究采用体外和体内模型评价苍术素对结直肠癌的抗癌治疗效果。MTT法检测苍术素对结肠癌细胞的细胞毒性，流式细胞术检测苍术素诱导的细胞凋亡。Western blotting检测裂解型caspase 3及其他凋亡蛋白的表达，探讨苍术素抗癌作用的机制。此外，我们还分析了PI3K/Akt/mTOR/p70S6K信号通路在苍术素诱导结肠癌细胞凋亡中的作用。本研究发现苍术素可引起剂量依赖性ros介导的结肠癌细胞凋亡和DNA损伤，并激活caspase 3。此外，苍术素通过靶向结肠癌细胞中的PI3Kγ抑制PI3K/Akt/mTOR/p70S6K信号通路。分子对接分析表明，苍术素与PI3Kγ的Akt结合口袋结合。本研究还评估了苍术素对结肠癌肿瘤异种移植模型的抗肿瘤作用，发现苍术素通过诱导细胞凋亡显著降低肿瘤生长和体积。这些结果表明，白术素有潜力作为治疗结直肠癌的候选药物，尽管还需要进一步的研究。图示:苍术素诱导结肠癌细胞凋亡。

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来源期刊

Macromolecular Research 工程技术-高分子科学

CiteScore

4.70

自引率

8.30%

发文量

100

审稿时长

1.3 months

期刊介绍： Original research on all aspects of polymer science, engineering and technology, including nanotechnology Presents original research articles on all aspects of polymer science, engineering and technology Coverage extends to such topics as nanotechnology, biotechnology and information technology The English-language journal of the Polymer Society of Korea Macromolecular Research is a scientific journal published monthly by the Polymer Society of Korea. Macromolecular Research publishes original researches on all aspects of polymer science, engineering, and technology as well as new emerging technologies using polymeric materials including nanotechnology, biotechnology, and information technology in forms of Articles, Communications, Notes, Reviews, and Feature articles.