Silencing of MGMT with small interference RNA reversed resistance in human BCUN-resistant glioma cell lines / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 2605-2610, 2011.
Artigo
em Inglês
| WPRIM
| ID: wpr-292836
ABSTRACT
<p><b>BACKGROUND</b>Our previous study had cloned two glioma cell lines SWOZ1 and SWOZ2 isolated from parental glioma cell line SWO38. The 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance of SWOZ1 was higher than that of SWOZ2. Since O6-methylguanine-DNA methyltransferase (MGMT) was thought to be closely related to BCNU resistance in glioma, this study aimed to explore the function of MGMT in glioma resistant to BCNU.</p><p><b>METHODS</b>A BCNU resistant glioma cell line SWOZ2-BCNU was established. The expression of MGMT was detected in SWOZ1, SWOZ2 and SWOZ2-BCNU. Small interferencing RNA targeting MGMT was used to silence the expression of MGMT in resistant cell lines SWOZ1 and SWOZ2-BCNU. The cytotoxicity of BCNU to these cells was measured using the cell counting kit-8 assay. Statistical analysis was carried out by one-way analysis of variance in statistical package SPSS 13.0.</p><p><b>RESULTS</b>The resistance of SWOZ1 and SWOZ2-BCNU against BCNU was 4.9-fold and 5.3-fold higher than that of SWOZ2. The results of quantitative RT-PCR and Western blotting confirmed that MGMT was both significantly increased in SWOZ1 and SWOZ2-BCNU compared to SOWZ2. After transfection with small interferencing RNA targeting MGMT, a decreased level of MGMT mRNA expression in SWOZ1 and SWOZ2-BCNU for more than 75% compared to negative control was found and confirmed by Western blotting. As a result, the resistance against BCNU was reversed for about 50% both in the BCNU-resistant cell lines SWOZ1 and SWOZ2-BCNU.</p><p><b>CONCLUSIONS</b>Silencing MGMT with specific small interferencing RNA can reverse the BCNU resistant phenotype in these glioma cell lines. MGMT may play an important role both in intrinsic and acquired BCNU-resistance in glioma.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Sincalida
/
Carmustina
/
Western Blotting
/
Resistencia a Medicamentos Antineoplásicos
/
O(6)-Metilguanina-DNA Metiltransferase
/
Reação em Cadeia da Polimerase Via Transcriptase Reversa
/
RNA Interferente Pequeno
/
Linhagem Celular Tumoral
/
Proliferação de Células
Limite:
Humanos
Idioma:
Inglês
Revista:
Chinese Medical Journal
Ano de publicação:
2011
Tipo de documento:
Artigo
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