P14ARF sensitizes human osteosarcoma cells to cisplatin-induced apoptosis in a p53-independent manner
| Autor: | Zi Bo Yang, Xiao Feng Zhu, Rong Deng, Gong Kan Feng, Ai Shan He, Xiu Fang Huang, Xiang Wei Yuan, Pu Yi Sheng, Wei Ming Liao |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Cell cycle checkpoint Antineoplastic Agents Apoptosis Bone Neoplasms Transfection p14arf Cell Line Tumor Tumor Suppressor Protein p14ARF medicine Humans fas Receptor Cytotoxicity Pharmacology Cisplatin Osteosarcoma Chemistry Proto-Oncogene Proteins c-mdm2 medicine.disease Cell biology Oncology Cell culture Cancer research Molecular Medicine Tumor Suppressor Protein p53 medicine.drug |
| Zdroj: | Cancer biologytherapy. 6(7) |
| ISSN: | 1538-4047 |
| Popis: | The tumor suppressor p14ARF, encoded by the INK4a/ARF locus, is often disrupted in human cancers, p14ARF triggers cell cycle arrest and sensitizes cells to apoptosis in the presence of collateral signals. To investigate the role of p14ARF in chemotherapeutic drugs-induced apoptosis, p14ARF was overexpressed by stable transfection in human osteosarcoma cell lines, U2OS (p53-wt/p14ARF-null) and MG63 (p53-mt/p14ARF-null). The results showed that ectopic p14ARF sensitized both cell lines to cisplatin-induced cytotoxicity and apoptosis. This sensitization of cisplatin-induced apoptosis was associated with upregulation of p53, Bax and p21 in U2OS cells. Conversely, such a result was not observed in MG63 cells. Moreover, the sensitization of cisplatin-induced cytotoxicity in U2OS cells was unaltered by p53 siRNA. Together, we show here p14ARF sensitizes human osteosarcoma cells to cisplatin-induced apoptosis in a p53-independent manner. Proper combinations of p14ARF gene transfer and conventional chemotherapy may be a valuable strategy in human osteosarcoma treatment. |
| Databáze: | OpenAIRE |
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