Growth inhibition by STI571 in combination with radiation in human chronic myelogenous leukemia K562 cells. - Institut Curie Accéder directement au contenu
Article Dans Une Revue Molecular Cancer Therapeutics Année : 2008

Growth inhibition by STI571 in combination with radiation in human chronic myelogenous leukemia K562 cells.

Résumé

Altered radiation responses by STI571 (Imatinib, Glivec), a specific inhibitor of the tyrosine kinase activity of Bcr-Abl, was assessed in K562 chronic myelogenous leukemia cells using growth inhibition and colony formation assays. Flow cytometry, Western blotting, and microscope observation were used to determine cell cycle redistribution, erythroid differentiation, apoptosis, necrosis, senescence, and expression and phosphorylation of effectors downstream from Bcr-Abl as endpoints. STI571 (> or =24-h contact) retarded the growth of K562 cells and elicited reduction in the G(2)-phase content due to an efficient arrest in early S phase rather than to the disruption of the G(2) checkpoint as confirmed by analysis of Lyn and CDK1 phosphorylation. STI571 brought about the inhibitory dephosphorylation of Bcr-Abl and STAT5, but the expression of DNA-PKcs and Rad51 was unaffected and the interaction between radiation and STI571 was strictly additive with regard to induction of apoptosis. Overall STI571 interacted cooperatively with radiation to retard the growth of K562 cells but did not affect intrinsic radiosensitivity. However, STI571 and radiation acted antagonistically with each other with regard to induction of senescence and erythroid differentiation.

Domaines

Chimie organique

Dates et versions

hal-00259181 , version 1 (27-02-2008)

Identifiants

Citer

Florence Huguet, Nicole Giocanti, Christophe Hennequin, Martine Croisy, Emmanuel Touboul, et al.. Growth inhibition by STI571 in combination with radiation in human chronic myelogenous leukemia K562 cells.. Molecular Cancer Therapeutics, 2008, 7 (2), pp.398-406. ⟨10.1158/1535-7163.MCT-07-2023⟩. ⟨hal-00259181⟩
45 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More