Ruipeng Song1, Ke Tian2, Weidong Wang3, Limin Wang4. 1. Bone Department, The First Affiliated Hospital of Zhengzhou University, China. Electronic address: 13810749892@163.com. 2. Bone Department, The First Affiliated Hospital of Zhengzhou University, China. Electronic address: 297634506@qq.com. 3. Bone Department, The First Affiliated Hospital of Zhengzhou University, China. Electronic address: sunmeizhongvip@163.com. 4. Bone Department, The First Affiliated Hospital of Zhengzhou University, China. Electronic address: wangliminvip12@163.com.
Abstract
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.
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.
Authors: Niyaz Zaman; Serena Santhana Dass; Persephone DU Parcq; Suzanne Macmahon; Lewis Gallagher; Lisa Thompson; Jamshid S Khorashad; Clara LimbÄck-Stanic Journal: Cancer Genomics Proteomics Date: 2020 Nov-Dec Impact factor: 4.069