Inhibition of Akt phosphorylation attenuates resistance to TNF-α cytotoxic effects in MCF-۷ cells, but not in their doxorubicin resistant derivatives
- سال انتشار: 1395
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 19، شماره: 12
- کد COI اختصاصی: JR_IJBMS-19-12_014
- زبان مقاله: انگلیسی
- تعداد مشاهده: 343
نویسندگان
Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Pharmaceutical Research Center, Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
چکیده
Objective(s): Acquisition of TNF-α resistance plays role in the onset and growth of malignant tumors. Previous studies have demonstrated that MCF-۷ cell line and its doxorubicin resistant variant MCF-۷/Adr are resistant against the cytotoxic effects of TNF-α. In this study, we investigated the role of Akt activation in resistance of MCF-۷ and MCF-۷/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 Ser۴۷۳ before and after ۷۲ hr TNF-α treatment was also determined by western blot. Results: TNF-α treatment led to enhancement of Akt Ser۴۷۳ phosphorylation. Treatment of MCF-۷ cells with TNF-α along with Akt-inhibitor agent, tricribine, attenuated Akt Ser۴۷۳ 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-۷/Adr cells alone or in combination with TNF-α. Conclusion: These results demonstrate that Akt phosphorylation plays pivotal role in the resistance of MCF-۷ cells against TNF-α-induced cytotoxicity while it might play no significant role in the resistance of MCF-۷/Adr cells against TNF-α.کلیدواژه ها
Akt, Breast carcinoma, Multidrug resistance, Protein kinase B, Tumor necrosis factor-alphaاطلاعات بیشتر در مورد COI
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