In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability
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 poorl...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2010-10-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010001000013 |
| _version_ | 1818334819247980544 |
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| author | A.O. Santos J.P. Pereira M.C. Pedroso de Lima S. Simões J.N. Moreira |
| author_facet | A.O. Santos J.P. Pereira M.C. Pedroso de Lima S. Simões J.N. Moreira |
| author_sort | A.O. Santos |
| collection | DOAJ |
| description | 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. |
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| id | doaj.art-eac5f97ea45b4773a8b1a013f7a3acc4 |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-12-13T14:13:35Z |
| publishDate | 2010-10-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-eac5f97ea45b4773a8b1a013f7a3acc42022-12-21T23:42:24ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2010-10-01431010011009In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viabilityA.O. SantosJ.P. PereiraM.C. Pedroso de LimaS. SimõesJ.N. MoreiraSmall 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010001000013Small cell lung cancerGene silencingBcl-2siRNAAntisense ODNFlow cytometryChemosensitization |
| spellingShingle | A.O. Santos J.P. Pereira M.C. Pedroso de Lima S. Simões J.N. Moreira In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability Brazilian Journal of Medical and Biological Research Small cell lung cancer Gene silencing Bcl-2 siRNA Antisense ODN Flow cytometry Chemosensitization |
| title | In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability |
| title_full | In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability |
| title_fullStr | In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability |
| title_full_unstemmed | In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability |
| title_short | In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability |
| title_sort | in vitro modulation of bcl 2 levels in small cell lung cancer cells effects on cell viability |
| topic | Small cell lung cancer Gene silencing Bcl-2 siRNA Antisense ODN Flow cytometry Chemosensitization |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010001000013 |
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