Cucurbitacin E inhibits osteosarcoma cells proliferation and invasion through attenuation of PI3K/AKT/mTOR signalling pathway.
Cucurbitacin E inhibits osteosarcoma cells proliferation and invasion through attenuation of PI3K/AKT/mTOR signalling pathway.
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DOI：
10.1042/bsr20160165
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发表时间：
2016-12
影响因子：
4
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Wang Y;Xu S;Wu Y;Zhang J
葫芦素E（Cucurbitacin E，CuE）是从植物中分离得到的一种三萜类化合物，具有抑制肿瘤细胞增殖、迁移和转移的作用。然而，CuE对骨肉瘤（OS）的作用和机制尚未完全了解。本研究旨在探讨CuE是否能抑制OS细胞的生长和侵袭，并揭示其分子机制。在不同浓度的CuE处理后，使用细胞计数Kit-8测定法评估CuE的抗增殖作用。流式细胞仪检测OS细胞凋亡情况。碘化丙啶染色分析细胞周期分布。Transwell法检测CuE对OS细胞侵袭能力的影响。通过蛋白质印迹法测定蛋白质水平。此外，在体内评估CuE对OS细胞生长抑制的效力。我们的研究结果表明，CuE抑制细胞的生长和侵袭，诱导细胞周期阻滞和触发凋亡，并调节细胞生长，细胞周期和细胞凋亡调节因子的表达。CuE通过抑制PI 3 K/Akt/mTOR信号通路和上皮-间质转化（EMT），抑制OS的侵袭和转移。综上所述，我们的研究表明，CuE可以通过抑制PI 3 K/Akt/mTOR信号通路来抑制OS肿瘤的生长和侵袭。我们的研究结果表明，CuE可以被认为是一个有前途的抗癌剂OS。
Cucurbitacin E (CuE), a potent member of triterpenoid family isolated from plants, has been confirmed as an antitumour agent by inhibiting proliferation, migration and metastasis in diverse cancer. However, the effects and mechanisms of CuE on osteosarcoma (OS) have not been well understood. The present study aimed to test whether CuE could inhibit growth and invasion of OS cells and reveal its underlying molecular mechanism. After various concentrations of CuE treatment, the anti-proliferative effect of CuE was assessed using the cell counting Kit-8 assay. Flow cytometry analysis was employed to measure apoptosis of OS cells. Cell cycle distribution was analysed by propidium iodide staining. Transwell assay was performed to evaluate the effect of CuE on invasion potential of OS cells. The protein levels were measured by western blot. In addition, the potency of CuE on OS cells growth inhibition was assessed in vivo. Our results showed that CuE inhibited cell growth and invasion, induced a cell cycle arrest and triggered apoptosis and modulated the expression of cell growth, cell cycle and cell apoptosis regulators. Moreover, CuE inhibited the PI3K/Akt/mTOR pathway and epithelial–mesenchymal transition (EMT), which suppressed the invasion and metastasis of OS. In addition, we also found that CuE inhibited OS cell growth in vivo. Taken together, our study demonstrated that CuE could inhibit OS tumour growth and invasion through inhibiting the PI3K/Akt/mTOR signalling pathway. Our findings suggest that CuE can be considered to be a promising anti-cancer agent for OS.