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 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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Gobin B,Battaglia S,Lanel R,Chesneau J,Amiaud J,Rédini F,Ory B,Heymann D

doi

10.1016/j.canlet.2013.11.017

subject

Has Abstract

pub_date

2014-03-28 00:00:00

pages

291-8

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(13)00827-6

journal_volume

344

pub_type

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