@article { author = {Ghandadi, Morteza and Mohammadi, Atieh and Behravan, Javad and Abnous, Khalil and Haj-Ali, Negin and Ehtesham Gharaee, Melika and Mosaffa, Fatemeh}, title = {Inhibition of Akt phosphorylation attenuates resistance to TNF-α cytotoxic effects in MCF-7 cells, but not in their doxorubicin resistant derivatives}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {19}, number = {12}, pages = {1363-1367}, year = {2016}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2016.7924}, abstract = {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.}, keywords = {Akt,Breast carcinoma,Multidrug resistance,Protein kinase B,Tumor necrosis factor-alpha}, url = {https://ijbms.mums.ac.ir/article_7924.html}, eprint = {https://ijbms.mums.ac.ir/article_7924_27366752e88cfa530bddf636eeaf709d.pdf} }