Document Detail


In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability.
MedLine Citation:
PMID:  20922271     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Small cell lung cancer (SCLC) is an aggressive disease, representing 15% of all cases of lung cancer, has high metastatic potential and low prognosis that urgently demands the development of novel therapeutic approaches. One of the proposed approaches has been the down-regulation of BCL2, with poorly clarified and controversial therapeutic value regarding SCLC. The use of anti-BCL2 small interfering RNA (siRNA) in SCLC has never been reported. The aim of the present study was to select and test the in vitro efficacy of anti-BCL2 siRNA sequences against the protein and mRNA levels of SCLC cells, and their effects on cytotoxicity and chemosensitization. Two anti-BCL2 siRNAs and the anti-BCL2 G3139 oligodeoxynucleotide (ODN) were evaluated in SCLC cells by the simultaneous determination of Bcl-2 and viability using a flow cytometry method recently developed by us in addition to Western blot, real-time reverse-transcription PCR, and cell growth after single and combined treatment with cisplatin. In contrast to previous reports about the use of ODN, a heterogeneous and up to 80% sequence-specific Bcl-2 protein knockdown was observed in the SW2, H2171 and H69 SCLC cell lines, although without significant sequence-specific reduction of cell viability, cell growth, or sensitization to cisplatin. Our results question previous data generated with antisense ODN and supporting the present concept of the therapeutic interest in BCL2 silencing per se in SCLC, and support the growing notion of the necessity of a multitargeting molecular approach for the treatment of cancer.
Authors:
A O Santos; J P Pereira; M C Pedroso de Lima; S Simões; J N Moreira
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-01
Journal Detail:
Title:  Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.]     Volume:  43     ISSN:  1414-431X     ISO Abbreviation:  Braz. J. Med. Biol. Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8112917     Medline TA:  Braz J Med Biol Res     Country:  Brazil    
Other Details:
Languages:  eng     Pagination:  1001-9     Citation Subset:  IM    
Affiliation:
University of Coimbra, Portugal.
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