Inhibition of Akt phosphorylation attenuates resistance to TNF-α cytotoxic effects in MCF-7 cells, but not in their doxorubicin resistant derivatives

• Main Authors: Morteza Ghandadi, Atieh Mohammadi, Javad Behravan, Khalil Abnous, Negin Haj-Ali, Melika Ehtesham Gharaee, Fatemeh Mosaffa
• Format: Article
• Language: English
• Published: Mashhad University of Medical Sciences 2016-12-01
• Series: Iranian Journal of Basic Medical Sciences
• Subjects: Akt; Breast carcinoma; Multidrug resistance; Protein kinase B; Tumor necrosis factor-alpha
• Online Access: http://ijbms.mums.ac.ir/article_7924_27366752e88cfa530bddf636eeaf709d.pdf

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.