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Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines
Authors:Mila Ljujic  Sanja Mijatovic  Mirna Z. Bulatovic  Marija Mojic  Danijela Maksimovic-Ivanic  Dragica Radojkovic  Aleksandra Topic
Affiliation:1.Institute of Molecular Genetics and Genetic Engineering,University of Belgrade,Belgrade,Serbia;2.Institute for Biological Research “Sinisa Stankovic”,University of Belgrade,Belgrade,Serbia;3.Department of Medical Biochemistry, Faculty of Pharmacy,University of Belgrade,Belgrade,Serbia
Abstract:
Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.
Keywords:
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