کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1951780 | 1055790 | 2006 | 6 صفحه PDF | دانلود رایگان |

The efficiency of anticancer therapy is often restricted by the development of drug resistance. Here, we report that the doxorubicin (DOX)-resistant MCF-7/Adr cells were more resistant to DOX-treatment than MCF-7 cells. However, an alternative treatment of DOX/TNF-α enhanced the cytotoxic effect in multidrug resistant MCF-7/Adr cell line. Treatment of cells with TNF-α following doxorubicin (DOX) resulted in a decrease of the activated Rel A/p65 in nuclei. Histone deacetylase 1 (HDAC1) was found to interact with Rel A/p65 in the complex, suggesting that HDAC1 is involved in mediating nuclear export of Rel A/p65. The combined treatment of TNF-α/DOX also resulted in a significant decrease of mRNA levels of anti-apoptotic genes, such as the cellular inhibitor of apoptosis-1 (c-IAP1), and the long isoform of B cell leukemia/lymphoma x gene (Bcl-xL), leading to efficient induction of caspase-8 cleavage and cell death. In previous work, we demonstrated that TNF-α promotes DOX-induced cell death and anti-cancer effect through downregulation of p21 in p53-deficient tumor cells. Thus, we proposed that alternative administration of TNF-α and DOX may be a new and efficient therapeutic strategy for patients that develop resistance to cytotoxic treatment.
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1763, Issue 2, February 2006, Pages 182–187