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大狼毒苷 D 通过 PI3K/Akt/mTOR 通路抑制骨肉瘤细胞增殖并诱导其凋亡。

Arnicolide D Inhibits Proliferation and Induces Apoptosis of Osteosarcoma Cells through PI3K/Akt/mTOR Pathway.

机构信息

Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.

出版信息

Anticancer Agents Med Chem. 2024;24(17):1288-1294. doi: 10.2174/0118715206289595240105082138.

Abstract

BACKGROUND

Osteosarcoma is considered as the most prevalent form of primary malignant bone cancer, prompting a pressing need for novel therapeutic options. Arnicolide D, a sesquiterpene lactone derived from the traditional Chinese herbal medicine (known as E Bu Shi Cao in Chinese), showed anticancer efficacy against several kinds of cancers. However, its effect on osteosarcoma remains unclear.

OBJECTIVE

This study aimed to investigate the anticancer activity of arnicolide D and the underlying molecular mechanism of its action in osteosarcoma cells, MG63 and U2OS.

METHODS

Cell viability and proliferation were evaluated through MTT assay and colony formation assay following 24 h and 48 h treatment with different concentrations of arnicolide D. Flow cytometry was employed to examine cell cycle progression and apoptosis after 24 h treatment of arnicolide D. Western blotting was performed to determine the expression of the PI3k, Akt and m-TOR and their phosphorylated forms.

RESULTS

Our findings revealed that arnicolide D treatment resulted in a significant reduction in cell viability, the inhibition of proliferation, and the induction of apoptosis and cell cycle arrest in the G2/M phase. Furthermore, arnicolide D could inhibit the activation of PI3K/Akt/mTOR pathway in osteosarcoma cells.

CONCLUSION

Based on our results, arnicolide D demonstrated significant anti-osteosarcoma activity and held the potential to be considered as a therapeutic candidate for osteosarcoma in the future.

摘要

背景

骨肉瘤被认为是原发性恶性骨癌中最常见的形式,因此迫切需要新的治疗选择。arnicolide D 是一种倍半萜内酯,来源于传统中药(在中国被称为 艾叶),对多种癌症具有抗癌作用。然而,其对骨肉瘤的作用尚不清楚。

目的

本研究旨在探讨 arnicolide D 的抗癌活性及其在骨肉瘤细胞 MG63 和 U2OS 中的作用机制。

方法

用不同浓度的 arnicolide D 处理 24 h 和 48 h 后,通过 MTT 法和集落形成实验评估细胞活力和增殖。用流式细胞术检测 arnicolide D 处理 24 h 后细胞周期进展和凋亡。用 Western blot 检测 PI3k、Akt 和 m-TOR 及其磷酸化形式的表达。

结果

我们的研究结果表明,arnicolide D 处理导致细胞活力显著降低,增殖受到抑制,并诱导凋亡和细胞周期阻滞在 G2/M 期。此外,arnicolide D 可以抑制骨肉瘤细胞中 PI3K/Akt/mTOR 通路的激活。

结论

基于我们的结果,arnicolide D 表现出显著的抗骨肉瘤活性,有潜力成为未来骨肉瘤的治疗候选药物。

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