title: 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.
authors: INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer 2012, Nantes 44035, France; Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumors, Nantes, France.
authors: Bérengère
authors: B
authors: Gobin
authors: INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer 2012, Nantes 44035, France; Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumors, Nantes, France.
authors: Séverine
authors: S
authors: Battaglia
authors: INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer 2012, Nantes 44035, France; Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumors, Nantes, France.
authors: Rachel
authors: R
authors: Lanel
authors: INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer 2012, Nantes 44035, France; Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumors, Nantes, France.
authors: Julie
authors: J
authors: Chesneau
authors: INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer 2012, Nantes 44035, France; Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumors, Nantes, France.
authors: Jérôme
authors: J
authors: Amiaud
authors: INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer 2012, Nantes 44035, France; Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumors, Nantes, France; Nanrtes University Hospital, rue Gaston Veil, 44035, Nantes, France.
authors: Françoise
authors: F
authors: Rédini
authors: INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer 2012, Nantes 44035, France; Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumors, Nantes, France.
authors: Benjamin
authors: B
authors: Ory
authors: INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer 2012, Nantes 44035, France; Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumors, Nantes, France; Nanrtes University Hospital, rue Gaston Veil, 44035, Nantes, France. Electronic address: dominique.heymann@univ-nantes.fr.
authors: Dominique
authors: D
authors: Heymann
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012516:Osteosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines / Q000494:pharmacology*; D011897:Random Allocation; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines; D058570:TOR Serine-Threonine Kinases; C531198:dactolisib
keywords: Osteosarcoma; PI3K Inhibitor; Pre-clinical model; Survival rate; mTOR Inhibitor