Document Detail


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.
MedLine Citation:
PMID:  21036697     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yohann Loriot; Pierre Mordant; Bob D Brown; Jean Bourhis; Jean-Charles Soria; Eric Deutsch
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  30     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2010-12-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3869-78     Citation Subset:  IM    
Affiliation:
UPRES 27-10, Institut Gustave Roussy, Villejuif, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects,  genetics,  radiation effects
Carcinoma, Small Cell / genetics,  metabolism,  radiotherapy,  therapy
Cell Line, Tumor
Cell Survival / drug effects,  genetics,  radiation effects
Combined Modality Therapy
Female
Humans
Lung Neoplasms / genetics,  metabolism,  radiotherapy,  therapy*
Mice
Mice, Nude
Oligonucleotides, Antisense / genetics,  pharmacokinetics,  pharmacology*
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*,  biosynthesis,  genetics
Thionucleotides / genetics,  pharmacokinetics,  pharmacology*
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Oligonucleotides, Antisense; 0/Proto-Oncogene Proteins c-bcl-2; 0/Thionucleotides; 0/oblimersen

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