Inhibition of BCL-2 in small cell lung cancer cell lines with oblimersen, an antisense BCL-2 oligodeoxynucleotide (ODN): in vitro and in vivo enhancement of radiation response.

Détails

ID Serval
serval:BIB_D9F4C2EB3936
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Inhibition of BCL-2 in small cell lung cancer cell lines with oblimersen, an antisense BCL-2 oligodeoxynucleotide (ODN): in vitro and in vivo enhancement of radiation response.
Périodique
Anticancer Research
Auteur(s)
Loriot Y., Mordant P., Brown B.D., Bourhis J., Soria J.C., Deutsch E.
ISSN
1791-7530 (Electronic)
ISSN-L
0250-7005
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
30
Numéro
10
Pages
3869-3878
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
BACKGROUND: Oblimersen, an ODN targeting BCL-2 RNA, has been shown to be effective in reducing BCL-2 expression in vitro and in in vivo models engineered to overexpress BCL-2. The present study evaluated the efficacy of combining BCL-2 ODN and radiation in small-cell lung cancers (SCLC) cell lines.
MATERIALS AND METHODS: The in vitro effect was determined using short term (cell viability) and long term (clonogenic) assays. Apoptosis, BCL-2 expression and intratumoural uptake of the FAM-ODN with or without prior radiation treatment were also evaluated. Combination of ODN and RT was also assessed in vivo.
RESULTS: Radiation was shown to increase intracellular and intratumoural penetration of oblimersen, confirming previous results obtained in prostate cancer xenograft models. Oblimersen decreased BCL-2 protein expression in vitro and in vivo. BCL-2 ODN sensitised H69 cells to radiation in vitro and in vivo. Oblimersen increased radiation-induced apoptosis and decreased in vivo tumoural vascularisation.
CONCLUSION: Oblimersen was shown to increase in vitro and in vivo effect of RT on SCLC cell lines. Radiation increases intracellular and intratumoural penetration of ODN. This pre-clinical study argues in favour of clinical development in localised SCLC.
Mots-clé
Animals, Apoptosis/drug effects, Apoptosis/genetics, Carcinoma, Small Cell/genetics, Carcinoma, Small Cell/metabolism, Cell Line, Tumor, Cell Survival/drug effects, Cell Survival/genetics, Combined Modality Therapy, Female, Humans, Lung Neoplasms/genetics, Lung Neoplasms/metabolism, Mice, Mice, Nude, Oligonucleotides, Antisense/genetics, Oligonucleotides, Antisense/pharmacokinetics, Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors, Proto-Oncogene Proteins c-bcl-2/biosynthesis, Thionucleotides/genetics, Thionucleotides/pharmacokinetics, Xenograft Model Antitumor Assays
Pubmed
Web of science
Création de la notice
01/12/2014 18:07
Dernière modification de la notice
03/03/2018 21:53
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