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Chinese Journal of Medical Genetics ; (6): 387-391, 2007.
Artículo en Chino | WPRIM | ID: wpr-247310

RESUMEN

<p><b>OBJECTIVE</b>To evaluate the relationship between mammalian target of rapamycin (mTOR) signaling pathway and histone acetylation in cell survival, cell cycle, gene expression and protein level on human gastric cancer cells.</p><p><b>METHODS</b>Human gastric cancer cell lines, MKN45 and SGC7901 were treated with trichostatin A, rapamycin and/or LY294002, a PI3K inhibitor. Cell viability was analyzed by methylthiazolyl tetrazolium. Cell cycle distribution was evaluated by flow cytometry. The transcription level of p21(WAF1) gene was detected by using real-time polymerase chain reaction. Proteins were detected by Western blotting.</p><p><b>RESULTS</b>Cell viability remarkably reduced after treatment by more than two drugs (P< 0.01). Through flow cytometry assessment, MKN45 cells were arrested in G2 phase (P< 0.05), while SGC7901 cells were in G2 or G1 phase (P< 0.05) whether treated with single or more than two drugs. The expression of p21(WAF1) mRNA was remarkably increased in the gastric cancer cells treated with conjoined drugs (P< 0.01). Phosphorylation of Akt, p70S6K and 4E-BP1 was significantly reduced in cells treated with conjoined drugs (P< 0.01). And histone acetylation of H4/H3 was also increased in cells treated with conjoined drugs (P< 0.01).</p><p><b>CONCLUSION</b>mTOR singnaling pathway has an important relationship with histone acetylation in gastric cancer cell lines. There is a co-effect of mTOR inhibitor and histone deacetylase inhibitor on gastric cancer cells.</p>


Asunto(s)
Humanos , Acetilación , Proteínas Adaptadoras Transductoras de Señales , Metabolismo , Western Blotting , Ciclo Celular , Línea Celular Tumoral , Supervivencia Celular , Cromonas , Farmacología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Genética , Citometría de Flujo , Histonas , Metabolismo , Ácidos Hidroxámicos , Farmacología , Morfolinas , Farmacología , Fosfoproteínas , Metabolismo , Fosforilación , Reacción en Cadena de la Polimerasa , Proteínas Quinasas , Metabolismo , Proteínas Proto-Oncogénicas c-akt , Metabolismo , ARN Mensajero , Genética , Metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Quinasas S6 Ribosómicas 70-kDa , Metabolismo , Transducción de Señal , Fisiología , Sirolimus , Farmacología , Neoplasias Gástricas , Metabolismo , Patología , Serina-Treonina Quinasas TOR
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