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


CONCLUSIONS
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.
Bone Department, The First Affiliated Hospital of Zhengzhou University, China. Electronic address: 13810749892@163.com.
Ruipeng
R
Song
Bone Department, The First Affiliated Hospital of Zhengzhou University, China. Electronic address: 297634506@qq.com.
Ke
K
Tian
Bone Department, The First Affiliated Hospital of Zhengzhou University, China. Electronic address: sunmeizhongvip@163.com.
Weidong
W
Wang
Bone Department, The First Affiliated Hospital of Zhengzhou University, China. Electronic address: wangliminvip12@163.com.
Limin
L
Wang
D020533:Angiogenesis Inhibitors; D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen; D004338:Drug Combinations; D006801:Humans; D007797:Laminin; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012516:Osteosarcoma / Q000098:blood supply / Q000201:enzymology* / Q000209:etiology / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011509:Proteoglycans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D003094:Collagen; D004338:Drug Combinations; D007797:Laminin; D019869:Phosphatidylinositol 3-Kinases; D011509:Proteoglycans; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53; C059485:matrigel; C546842:MTOR protein, human
Invasion; MG63; Mammalian target of rapamycin (mTOR); Migration; Osteosarcoma; P53; PI3K/AKT/mTOR pathway; Target therapy