Rosiglitazone enhances 5-fluorouracil-induced cell growth inhibition in hepatocellular carcinoma cell line Hep3B / 癌症
Chinese Journal of Cancer
; (12): 741-746, 2010.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-296360
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>BACKGROUND AND OBJECTIVE</b>Rosiglitazone is a peroxisome proliferators-activated receptor gamma (PPARgamma) ligand, which inhibits tumor growth by activating PPARgamma signaling pathways. Fluorouracil (5-FU) is one of the commonly used chemotherapeutic drugs. However, patients develop drug resistance of 5-FU over time. The aim of this study was to investigate whether rosiglitazone can enhance 5-FU-induced cell growth inhibition and to explore its potential mechanisms.</p><p><b>METHODS</b>Cell viability was measured using MTT assay. Protein expression levels were detected by Western blot analysis. Small interference RNA was utilized to knockout PPARgamma and PTEN in Hep3B cells.</p><p><b>RESULTS</b>After 48 h of treatment with 10, 20, and 40 µmol/L rosiglitazone, the viability of Hep3B cells was (78.0 ± 2.7)%, (37.3 ± 8.1)%, and (19.8 ± 2.2)%, respectively (compared with control group, P values were all < 0.001). After 48 h of treatment with 10 µmol/L 5-FU, the viability of Hep3B cells was about (82.6 ± 3.9)%. When cells were treated with 10 µmol/L 5-FU in combination with either 10, 20 or 40 µmol/L rosiglitazone, the cell viability was (51.6 ± 5.4)%, (14.8 ± 4.2)%, and (8.5 ± 0.9)%, with corresponding q value of 1.36, 1.23, and 1.19, respectively. These data suggested that the two drugs had synergic effect in inhibiting Hep3B cell growth, which was further confirmed in an in vivo mice model. Subsequent investigations showed that rosiglitazone activated PPARgamma signaling pathways and increased the expression of PTEN.</p><p><b>CONCLUSIONS</b>Rosiglitazone enhances 5-FU-induced cell growth inhibition of Hep3B cells.</p>
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Farmacologia
/
Transdução de Sinais
/
Carcinoma Hepatocelular
/
Inativação Gênica
/
RNA Interferente Pequeno
/
Linhagem Celular Tumoral
/
Tiazolidinedionas
/
PPAR gama
/
Carga Tumoral
Limite:
Animais
/
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Chinese Journal of Cancer
Ano de publicação:
2010
Tipo de documento:
Artigo