@article{APS3674,
author = {Xiang-wei Yuan and Xiao-feng Zhu and Xiu-fang Huang and Pu-yi Sheng and Ai-shan He and Zi-bo Yang and Rong Deng and Gong-kan Feng and Wei-ming Liao},
title = {Interferon-α enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis},
journal = {Acta Pharmacologica Sinica},
volume = {28},
number = {11},
year = {2016},
keywords = {},
abstract = {Aim: To determine whether interferon-α (IFNα) can enhance doxorubicin sensitivity in osteosarcoma cells and its molecular mechanism.
Methods: Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was studied using Flow cytometry analysis, Hoechst33258 staining, DNA fragmentation assay, as well as the activation of caspase-3 and poly (ADP-ribose) polymerase. Protein expression was detected by Western blotting. The dependence of p53 was determined using p53-siRNA transfection.
Results: IFNα increased doxorubicin-induced cytotoxicity to a much greater degree through apoptosis in human osteosarcoma p53-wild U2OS cells, but not p53-mutant MG63 cells. IFNα markedly upregulated p53, Bax, Mdm2, and p21, downregulated Bcl-2, and activated caspase-3 and PARP cleavage in response to doxorubicin in U2OS cells. Moreover, the siRNA-mediated silencing of p53 significantly reduced the IFNα/doxorubicin combination-induced cytotoxic-ity and PARP cleavage.
Conclusion: IFNα enhances the sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis. The proper combination with IFNα and conventional chemotherapeutic agents may be a rational strategy for improving the treatment of osteosarcoma with functional p53.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3674}
}