磷酸肌醇3激酶／蛋白激酶B／哺乳动物雷帕霉素靶蛋白信号通路下p53基因对骨肉瘤细胞增殖及转移的抑制作用

Inhibitory effect of p53 on proliferation and metastasis of osteosarcoma via the phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin pathway

目的观察p53基因对骨肉瘤细胞增殖和迁移能力影响并探讨其可能机制。方法使用细胞计数试剂盒（CCK-8）对p53的抑制增殖作用进行评估。分别使用划痕法和侵袭小室法（Transwell）分析其转移和侵袭潜能。最终应用免疫组织化学对S2448p哺乳动物雷帕霉素靶蛋白（mTOR）的表达进行探测。结果MG63细胞株和hFOB细胞株在p53浓度为100 nmol/L时，划痕愈合率（%）分别为22.37±1.35和76.84±0.97；侵袭抑制定量结果分别为417.35±3.67和386.54±2.78。体内p53基因在50～500 nmol/L的半数抑制浓度范围内能够有效抑制骨肉瘤细胞株（MG63）和人体正常成骨细胞株（hFOB1.19）的细胞增殖。结论p53基因能够通过磷酸肌醇3激酶/蛋白激酶B/mTOR信号通路抑制骨肉瘤的细胞增殖并降低迁移的可能。

Objective Objective To investigate the role of p53 in the pathogenesis of osteosarcoma and the possible mechanism.MethodsThe anti-proliferative effect of p53 was assessed using the cell counting kit-8 （CCK-8） assay. The migration and invasion potentials were analyzed using wound-healing and Transwell assays, respectively. Finally, S2448p-mammalian target of rapamycin （mTOR） expression was detected in osteosarcoma tissues using immunohistochemistry.ResultsThe wound healing rate （%） of MG63 and hFOB cells was 22.37±1.35 and 76.84±0.97, respectively, at a p53 concentration of 100 nmol/L. At the same concentration, the quantitative results of invasion inhibition were 417.35±3.67 and 386.54±2.78, respectively. p53 potently inhibited cell proliferation MG63 and hFOB1.19 cells in vitro at the half maximal inhibitory concentration （IC50） ranging from 50 to 500 nmol/L.ConclusionThese results show that p53 suppresses cell proliferation of osteosarcoma through inhibition of the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt）/mTOR pathway, which might be an effective novel therapeutic candidate against osteosarcoma in the future.