P53 suppresses cell proliferation, metastasis, and angiogenesis of osteosarcoma through inhibition of the PI3K/AKT/mTOR pathway

INTERNATIONAL JOURNAL OF SURGERY

卷:20

Article

Song, Ruipeng¹  Tian, Ke¹  Wang, Weidong¹  Wang, Limin¹ 

[1] Zhengzhou Univ, Affiliated Hosp 1, Bone Dept, Zhengzhou, Peoples R China

关键词: Osteosarcoma;    MG63;    P53;    Mammalian target of rapamycin (mTOR);    PI3K/AKT/mTOR pathway;    Invasion;    Migration;    Target therapy;   

DOI  :  10.1016/j.ijsu.2015.04.050

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free