Interferon-α enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis
| Autor: | Gong Kan Feng, Rong Deng, Zi Bo Yang, Pu Yi Sheng, Wei Ming Liao, Xiang Wei Yuan, Xiu Fang Huang, Ai Shan He, Xiao Feng Zhu |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Transcriptional Activation
Cell Survival Apoptosis In Vitro Techniques Flow cytometry Interferon Cell Line Tumor medicine Humans Pharmacology (medical) Doxorubicin Viability assay Cytotoxicity Pharmacology Osteosarcoma Antibiotics Antineoplastic medicine.diagnostic_test business.industry Interferon-alpha Drug Synergism General Medicine Transfection Genes p53 Molecular biology Mutation DNA fragmentation business medicine.drug |
| Zdroj: | Acta Pharmacologica Sinica. 28:1835-1841 |
| ISSN: | 1745-7254 1671-4083 |
| DOI: | 10.1111/j.1745-7254.2007.00662.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text