Academic Journal
The anti-tumoral effect of lenalidomide is increased in vivo by hypoxia-inducible factor (HIF)-1α inhibition in myeloma cells.
| العنوان: | The anti-tumoral effect of lenalidomide is increased in vivo by hypoxia-inducible factor (HIF)-1α inhibition in myeloma cells. |
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| المؤلفون: | Storti, Paola, Toscani, Denise, Airoldi, Irma, Marchica, Valentina, Maiga, Sophie, Bolzoni, Marina, Fiorini, Elena, Campanini, Nicoletta, Martella, Eugenia, Mancini, Cristina, Guasco, Daniela, Ferri, Valentina, Donofrio, Gaetano, Aversa, Franco, Amiot, Martine, Giuliani, Nicola |
| المساهمون: | Department of Clinical and Experimental Medicine, Università degli studi di Parma = University of Parma (UNIPR), Laboratorio di Oncologia, Istituto Giannina Gaslini, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Azienda Ospedaliero-Universitaria of Parma, Department of Biotechnology and Life Sciences, Universitá degli Studi dell’Insubria = University of Insubria Varese (Uninsubria), Department of Medical-Veterinary Science, This work was supported in part by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG2014 n°15531 (NG). |
| المصدر: | ISSN: 0390-6078. |
| بيانات النشر: | HAL CCSD Ferrata Storti Foundation |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | International audience ; The anti-tumoral effect of lenalidomide is increased in vivo by hypoxia-inducible factor (HIF)-1α inhibition in myeloma cells We investigated the effect of stable suppression of hypoxia inducible factor (HIF)-1α in myeloma cells on sensitivity to lenalidomide (LEN) in vivo. We found that the in vivo anti-tumoral effect of LEN is enhanced by HIF-1α suppression in myeloma cells. It has been reported that HIF-1α is over-expressed by myeloma cells 1-4 and that HIF-1α suppression significantly blocks myeloma-induced angiogenesis, and reduces both tumoral burden and bone destruction in vivo in multiple myeloma (MM) mouse models. 3 The potential effects of HIF-1α modulation on drug sensitivity in MM cells are not known and are currently under investigation. The immunomodulatory drugs (IMiDs®), including LEN, are a class of drugs derived from thalidomide 4 able to exert anti-myeloma effects by the selective Cereblon-dependent destruction of IKZF proteins, 5,6 either through a direct action on MM cell proliferation and survival, 7 or through indirect immunomodulatory and anti-angiogenic effects. 7 Previous data indicated that HIF-1α inhibition did not increase the anti-proliferative in vitro effect of bortezomib on MM cells; 2,3 this drug induces a strong downregula-tion of HIF-1α in MM cells. 2 We recently reported that HIF-1α knockdown in the human myeloma cell line (HMCL) JJN3 potentiated the in vitro effect of LEN treatment (48-72 h) on cell proliferation through a significant upregulation of p27 without changing cell viability. 3 It has been consistently reported that LEN only slightly down-regulated HIF-1α expression in MM cells. 2 Such evidence has provided the rationale to investigate the effect of stable suppression of HIF-1α in myeloma cells on LEN sensitivity in vivo. Therefore, in the present study, we first inhibited HIF-1α in three HMCLs (JJN3, OPM2 and H929) using an anti-HIF1α lentiviral shRNA pool, as previously described. 3 H929 showed a very high mortality rate after anti-HIF1α ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/26659917; inserm-01285193; https://inserm.hal.science/inserm-01285193; https://inserm.hal.science/inserm-01285193/document; https://inserm.hal.science/inserm-01285193/file/giuliani_amiot.pdf; PUBMED: 26659917 |
| DOI: | 10.3324/haematol.2015 |
| الاتاحة: | https://inserm.hal.science/inserm-01285193 https://inserm.hal.science/inserm-01285193/document https://inserm.hal.science/inserm-01285193/file/giuliani_amiot.pdf https://doi.org/10.3324/haematol.2015 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.7BF3DAEA |
| قاعدة البيانات: | BASE |
| DOI: | 10.3324/haematol.2015 |
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