TAT-RasGAP317-326 Enhances Radiosensitivity of Human Carcinoma Cell Lines In Vitro and In Vivo through Promotion of Delayed Mitotic Cell Death.

Détails

ID Serval
serval:BIB_13F935643BF3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TAT-RasGAP317-326 Enhances Radiosensitivity of Human Carcinoma Cell Lines In Vitro and In Vivo through Promotion of Delayed Mitotic Cell Death.
Périodique
Radiation research
Auteur(s)
Tsoutsou P., Annibaldi A., Viertl D., Ollivier J., Buchegger F., Vozenin M.C., Bourhis J., Widmann C., Matzinger O.
ISSN
1938-5404 (Electronic)
ISSN-L
0033-7587
Statut éditorial
Publié
Date de publication
05/2017
Peer-reviewed
Oui
Volume
187
Numéro
5
Pages
562-569
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article
Publication Status: ppublish
Résumé
The synthetic peptide TAT-RasGAP317-326 has been shown to potentiate the efficacy of anti-cancer drugs. In this study, we explored the action of TAT-RasGAP317-326 when combined with radiation by investigating its radiosensitizing activity in vitro and in vivo. To investigate the modulation of intrinsic radiosensitivity induced by TAT-RasGAP317-326, clonogenic assays were performed using four human cancer cell lines, HCT116 p53(+/+) (ATCC: CCL-247), HCT116 p53(-/-), PANC-1 (ATCC: CRL-1469) and HeLa (ATCC: CCL-2), as well as one nontumor cell line, HaCaT (CLS: 300493). Next, to investigate tumor growth delay after irradiation, HCT116 cell lines were selected and xenografted onto nude mice that were then treated with TAT-RasGAP317-326 alone or in combination with radiation or cisplatin. Afterwards, cell cycle and death modulation were investigated by quantification of micronuclei and apoptosis-related protein array. TAT-RasGAP317-326 radiosensitized all four human carcinoma cell lines tested but displayed no effect on normal cells. It also displayed no effect when administered as monotherapy. This radiosensitizing effect was confirmed in vivo in both p53-positive and p53-negative HCT116 xenografts. TAT-RasGAP317-326 combined with radiation enhanced the number of cells in S phase and subsequently delayed cell death, but had almost no effect on major apoptosis-related proteins. TAT-RasGAP317-326 is a radiosensitizing agent that acts on carcinoma cells and its radiosensitizing effect might be mediated, at least in part, by the enhancement of mitotic cell death.

Mots-clé
Apoptosis/drug effects, Apoptosis/radiation effects, Cell Line, Tumor, Dose-Response Relationship, Drug, GTPase-Activating Proteins/administration & dosage, HCT116 Cells, HeLa Cells, Humans, Mitosis/drug effects, Mitosis/radiation effects, Neoplasms, Experimental/pathology, Neoplasms, Experimental/radiotherapy, Peptide Fragments/administration & dosage, Radiation Tolerance/drug effects, Radiation-Sensitizing Agents/administration & dosage, Radiotherapy Dosage, Treatment Outcome
Pubmed
Web of science
Création de la notice
28/03/2017 16:54
Dernière modification de la notice
20/08/2019 12:42
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