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藤黄酸通过诱导细胞凋亡和细胞周期阻滞抑制骨肉瘤细胞的体外生长。

Gambogic acid inhibits the growth of osteosarcoma cells in vitro by inducing apoptosis and cell cycle arrest.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, PR China.

出版信息

Oncol Rep. 2011 May;25(5):1289-95. doi: 10.3892/or.2011.1189. Epub 2011 Feb 17.

Abstract

The natural product gambogic acid (GA) has been demonstrated to be a promising chemotherapeutic drug for some cancers because of its ability to induce apoptosis and cell cycle arrest. Until now, no studies have looked at the role of GA in osteosarcoma. In this study, we observed the effects of GA on the growth and apoptosis of osteosarcoma cells in vitro. We found that GA treatment inhibits the proliferation of osteosarcoma cells by inducing cell cycle arrest. Moreover, we found that GA induces apoptosis in MG63, HOS and U2OS cells. Furthermore, we showed that GA treatment elevates the Bax/Bcl-2 ratio. GA mediated the G0/G1 phase arrest in U2OS cells; this arrest was associated with a decrease in phospho-GSK3-β (Ser9) and the expression of cyclin D1. Similarly, in MG63 cells, GA mediated G2/M cell cycle arrest, which was associated with a decrease in phospho-cdc2 (Thr 161) and cdc25B. Overall, our findings suggest that GA may be an effective anti-osteosarcoma drug because of its capability to inhibit proliferation and induce apoptosis of osteosarcoma cells.

摘要

天然产物藤黄酸(GA)因其能够诱导细胞凋亡和细胞周期停滞而被证明是一种有前途的化疗药物,可用于治疗某些癌症。到目前为止,还没有研究探讨 GA 在骨肉瘤中的作用。在这项研究中,我们观察了 GA 对骨肉瘤细胞体外生长和凋亡的影响。我们发现,GA 通过诱导细胞周期停滞来抑制骨肉瘤细胞的增殖。此外,我们发现 GA 诱导 MG63、HOS 和 U2OS 细胞凋亡。此外,我们表明 GA 处理可提高 Bax/Bcl-2 比值。GA 介导 U2OS 细胞 G0/G1 期阻滞;这种阻滞与磷酸化 GSK3-β(Ser9)和 cyclin D1 表达减少有关。同样,在 MG63 细胞中,GA 介导 G2/M 细胞周期阻滞,与磷酸化 cdc2(Thr 161)和 cdc25B 的减少有关。总的来说,我们的研究结果表明,GA 可能是一种有效的抗骨肉瘤药物,因为它能够抑制骨肉瘤细胞的增殖并诱导其凋亡。

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