NVP-BEZ235, a dual PI3K/mTOR inhibitor, inhibits osteosarcoma cell proliferation and tumor development in vivo with an improved survival rate

Abstract 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 inh...

Full description

Saved in:
Bibliographic Details
Published in:Cancer letters 2014-03, Vol.344 (2), p.291-298
Main Authors: Gobin, Bérengère, Battaglia, Séverine, Lanel, Rachel, Chesneau, Julie, Amiaud, Jérôme, Rédini, Françoise, Ory, Benjamin, Heymann, Dominique
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Bone Neoplasms - drug therapy
Bone Neoplasms - enzymology
Bone Neoplasms - pathology
Cancer
Cell Growth Processes - drug effects
Cell Line, Tumor
Hematology, Oncology and Palliative Medicine
Humans
Imidazoles - pharmacology
Life Sciences
Male
Mice
Mice, Inbred C57BL
Mice, Nude
mTOR Inhibitor
Osteosarcoma
Osteosarcoma - drug therapy
Osteosarcoma - enzymology
Osteosarcoma - pathology
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Phosphatidylinositol 3-Kinases - metabolism
PI3K Inhibitor
Pre-clinical model
Quinolines - pharmacology
Random Allocation
Survival rate
TOR Serine-Threonine Kinases - antagonists & inhibitors
TOR Serine-Threonine Kinases - metabolism
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract 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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2013.11.017