inhibition of akt phosphorylation attenuates resistance to tnf-α cytotoxic effects in mcf-7 cells, but not in their doxorubicin resistant derivatives

objective(s): acquisition of tnf-α resistance plays role in the onset and growth of malignant tumors. previous studies have demonstrated that mcf-7 cell line and its doxorubicin resistant variant mcf-7/adr are resistant against the cytotoxic effects of tnf-α. in this study, we investigated the role of akt activation in resistance of mcf-7 and mcf-7/adr against tnf-α cytotoxicity. materials and methods: the role of akt activation in tnf-α cytotoxicity was investigated by mtt cell viability assay following treatment of the cells with the chemical inhibitor of akt activation with or without tnf-α treatment. phosphorylation of akt at ser473 before and after 72 hr tnf-α treatment  was also determined by western blot. results: tnf-α treatment led to enhancement of akt ser473 phosphorylation. treatment of mcf-7 cells with tnf-α along with akt-inhibitor agent, tricribine, attenuated akt ser473 phosphorylation and sensitized these cells to the cytotoxic effects of tnf-α in a dose and time dependent manner while tricribine treatment did not cause any significant cytotoxicity in mcf-7/adr cells alone or in combination with tnf-α. conclusion: these results demonstrate that akt phosphorylation plays pivotal role in the resistance of mcf-7 cells against tnf-α-induced cytotoxicity while it might play no significant role in the resistance of mcf-7/adr cells against tnf-α.