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Anticancer Res ; 30(9): 3557-64, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20944137

RESUMEN

AIM: To determine whether increasing p53 protein levels confers enhanced chemosensitivity in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Three NSCLC cell lines, with different endogenous p53 expression, were transfected with wild-type p53 (wt-p53) or CD-1 (truncated wt-p53) genes. Cells were subsequently treated with cisplatin (CDDP) or paclitaxel (PAX). Cell viability was measured using Alamar Blue Assay. RESULTS: Cells transfected with CD-1 expressed 13-38% higher levels of p53 protein compared to cells transfected with the wt-p53 gene, despite their baseline endogenous levels. CD-1-transfected cells also had higher cell death when treated with CDDP (p<0.05) or PAX, exhibiting 30-60% higher death rates than cells transfected with the wt-p53 gene and 130-160% higher than untransfected cells. A significant positive correlation between p53 protein concentration and cytotoxic response was demonstrated (R(2) for CDDP=0.823; R(2) for PAX=0.909; p<0.001). CONCLUSION: Increasing intracellular p53 protein concentrations can augment the effect of CDDP and PAX in NSCLC, despite the baseline level of p53 protein expression.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Resistencia a Antineoplásicos/genética , Neoplasias Pulmonares/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cisplatino/farmacología , Ensayo de Inmunoadsorción Enzimática , Humanos , Neoplasias Pulmonares/genética , Paclitaxel/farmacología , Transfección , Proteína p53 Supresora de Tumor/genética
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