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Int J Mol Sci ; 13(5): 6521-6533, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22754381

RESUMEN

Drug resistance is a major factor for the limited efficacy of chemotherapy in gastric cancer treatment. Hypoxia-inducible factor-1α (HIF-1α), a central transcriptional factor in hypoxia, is suggested to participate in the resistance. Here, we identified a hypoxia-mimic (cobalt chloride) sensitive gastric cell line BGC-823 to explore whether diosgenin, an aglycone of steroidal saponins, can inhibit cancer cell invasion and survival of solid tumor in a hypoxic mimic microenvironment. We have shown that diosgenin is a potent candidate for decreasing the ability of invasion and survival in cobalt chloride treated BGC-823 cells. In addition, when combined with HIF-1α specific short hairpin RNA (shRNA), diosgenin can inhibit BGC-823 cells more effectively. The anti-invasion role of diosgenin may be related to E-cadherin, integrinα5 and integrin ß6. These results suggest that diosgenin may be a useful compound in controlling gastric cancer cells in hypoxia condition, especially when combined with down-regulated HIF-1α.


Asunto(s)
Cobalto/farmacología , Diosgenina/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , ARN Interferente Pequeño/metabolismo , Neoplasias Gástricas/metabolismo , Cadherinas/genética , Cadherinas/metabolismo , Hipoxia de la Célula/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Integrina alfa5/genética , Integrina alfa5/metabolismo , Cadenas beta de Integrinas/genética , Cadenas beta de Integrinas/metabolismo , Invasividad Neoplásica , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología
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