Study on the mechanism of DDP-resistance mediated by phosphate JNK in gastric cancer / 中华胃肠外科杂志
Chinese Journal of Gastrointestinal Surgery
; (12): 159-162, 2008.
Article
em Zh
| WPRIM
| ID: wpr-273871
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism of DDP-resistance in gastric cancer cell line SGC7901/DDP mediated by phosphate(p)-JNK.</p><p><b>METHODS</b>The p-JNK expression was blocked by the JNK inhibitor SP600125. The drug sensitivity was detected by MTT. Cell apoptosis rate was measured by flow cytometry. The expression of p-JNK and P-glycoprotein (P-gp) was examined by Western blot. The expression of both proteins were detected in a tissue microarray containing 168 spots of cancer tissue and 27 spots of normal gastric tissue by SP immunohistochemistry. Pearson method was used to analyze the correlation between p-JNK and P-gp.</p><p><b>RESULTS</b>The drug sensitivity and cell apoptosis rate significantly increased (P<0.01), and the protein expression levels of p-JNK and P-glycoprotein were down-regulated after the inhibition of p-JNK by SP600125 in both SGC7901(p-JNK: 1.17+/-0.03 vs 0.38+/-0.071, P-gp: 0.21+/-0.01 vs 0.06+/-0.01) and SGC7901/DDP (p-JNK: 2.56+/-0.14 vs 1.02+/-0.12, P-gp: 0.77+/-0.05 vs 0.52+/-0.06 )cells(all P<0.01). The protein expression rates of p-JNK and P-glycoprotein were 45.8% and 51.8% respectively in gastric cancer tissue, which were significantly higher than those in normal gastric tissue 7.4% and 18.5% (P<0.01). The correlation of protein expression of p-JNK and P-gp was positive (P<0.01).</p><p><b>CONCLUSION</b>JNK anti-apoptosis pathway with the regulation of P-gp expression plays an important role in the DDP-resistance of gastric cancer, which may be a novel target for reversing multidrug resistance.</p>
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Índice:
WPRIM
Assunto principal:
Farmacologia
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Neoplasias Gástricas
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Transdução de Sinais
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Regulação Neoplásica da Expressão Gênica
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Cisplatino
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Apoptose
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Resistência a Múltiplos Medicamentos
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Resistencia a Medicamentos Antineoplásicos
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Linhagem Celular Tumoral
Limite:
Humans
Idioma:
Zh
Revista:
Chinese Journal of Gastrointestinal Surgery
Ano de publicação:
2008
Tipo de documento:
Article