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Inhibition of poly (ADP-ribose) polymerase-1 enhances doxorubicin activity against liver cancer cells.

Cancer letters (2010-11-26)
J A Muñoz-Gámez, R Quiles-Pérez, A Ruiz-Extremera, A B Martín-Álvarez, Laura Sanjuan-Nuñez, A Carazo, Josefa León, F J Oliver, J Salmerón
RÉSUMÉ

The purpose of this study was to investigate whether PARP-1 inhibition sensitizes human liver cancer cell lines to doxorubicin treatment. Both the addition of PARP-1 inhibitor (ANI) and depletion by means of stable siRNA significantly enhanced the growth inhibition induced by the DNA damage agents used. This effect was associated with an accumulation of unrepaired DNA, with a reduction in EGFR and Bcl-xL gene expression as well as with positive annexin-V staining. These results provide novel evidence of the direct role of PARP-1 in tumour chemoresistance in relation to its effects on the transcription of key genes involved in tumour survival.

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4-Amino-1,8-naphthalimide