期刊
CANCER LETTERS
卷 344, 期 2, 页码 291-298出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.11.017
关键词
PI3K Inhibitor; mTOR Inhibitor; Survival rate; Pre-clinical model; Osteosarcoma
类别
资金
- Region des Pays de la Loire
- INSERM
Despite recent improvements in chemotherapy and surgery, the problem of non-response osteosarcoma to chemotherapy remains, and is a parameter that is critical for prognosis. The present work investigated the therapeutic value of NVP-BEZ235, a dual class I PI3K/mTOR inhibitor. NVP-BEZ235 inhibited osteosarcoma cell proliferation by inducing G0/G1 cell cycle arrest with no caspase activation. In murine pre-clinical models, NVP-BEZ235 significantly slowed down tumor progression and ectopic tumor bone formation with decreased numbers of Ki67(+) cells and reduced tumor vasculature. Finally, NVP-BEZ235 considerably improved the survival rate of mice with osteosarcoma. Taken together, the results of the present work show that NVP-BEZ235 exhibits therapeutic interest in osteosarcoma and may be a promising adjuvant drug for bone sarcomas. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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