P53 suppresses cell proliferation, metastasis, and angiogenesis of osteosarcoma through inhibition of the PI3K/AKT/mTOR pathway
P53 suppresses cell proliferation, metastasis, and angiogenesis of osteosarcoma through inhibition of the PI3K/AKT/mTOR pathway
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DOI：
10.1016/j.ijsu.2015.04.050
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发表时间：
2015-08-01
影响因子：
15.3
通讯作者：
Wang, Limin
中科院分区：
文献类型：
--
作者：
Song, Ruipeng;Tian, Ke;Wang, Limin
目的：探讨P53在骨肉瘤发病机制中的作用及其可能的机制。方法：采用细胞计数Kit-8法检测P53的抗增殖作用。分别用伤口愈合试验和穿孔试验分析细胞的迁移和侵袭能力。Matrigel毛细血管形成实验模拟体内血管生成。免疫印迹法和免疫荧光法观察肌动蛋白纤维的蛋白表达和分布。结果：首先，P53对骨肉瘤细胞(MG63)和人成骨细胞(hFOB1.19)具有明显的抑制细胞增殖作用，IC50范围为50~500nmol/L；其次，P53对骨肉瘤细胞株MG63的转移有抑制作用，并抑制了AKT和mTOR等PI3K下游因子的细胞骨架重排和磷酸化。结论：P53通过抑制PI3K/AKT/mTOR通路抑制骨肉瘤细胞的增殖和血管生成有望成为未来治疗骨肉瘤的有效新候选药物。(C)爱思唯尔有限公司代表ijs出版集团有限公司出版的《2015》。
Objective: To investigate the role of P53 in the pathogenesis of osteosarcoma and the possible mechanism involved in it.Methods: The anti-proliferative effect of P53 was assessed using the cell counting Kit-8 assay. The migration and invasion potential were analyzed using wound-healing and transwell assays, respectively. The Matrigel capillary tube formation assay was performed to mimic in-vivo angiogenesis. Immunoblotting and immunofluorescence were used to observe protein levels and distribution of actin fibers. Finally, S2448p-mammalian target of rapamycin (mTOR) expression was detected on osteosarcoma tissues using immunohistochemistry.Results: Firstly, P53 potently inhibited cell proliferation in osteosarcoma cell line (MG63) and in human normal osteoblasts (hFOB1.19) in vitro at the IC50 ranged from 50 to 500 nmol/l. Then, an inhibitory effect of P53 on metastasis was observed in osteosarcoma cell line MG63, along with the cytoskeletal rearrangements and suppression of the phosphorylation of PI3K downstream factors including AKT and mTOR.Conclusion: These results show that P53 suppresses cell proliferation and angiogenesis of osteosarcoma through inhibition of the PI3K/AKT/mTOR pathway, which might be an effective novel therapeutic candidate against osteosarcoma in the future. (C) 2015 Published by Elsevier Ltd on behalf of IJS Publishing Group Limited.