Adenovirus-mediated p16 transfer to glioma cells induces G1 arrest and protects from paclitaxel and topotecan: implications for therapy
| Autor: | W. K. A. Yung, V. K. Puduvalli, Candelaria Gomez-Manzano, V. A. Levin, R. Perez-Soler, Pilar Martin-Duque, Athanassios P. Kyritsis, Juan Fueyo |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Cancer Research
Time Factors Paclitaxel Cell Division/drug effects medicine.medical_treatment Antineoplastic Agents Cell Cycle/drug effects Biology Transfection Adenoviridae chemistry.chemical_compound Glioma/*drug therapy Glioma Cyclin-Dependent Kinase Inhibitor p16/biosynthesis/*metabolism medicine Humans Recombinant Proteins/biosynthesis Cyclin-Dependent Kinase Inhibitor p16 Chemotherapy Dose-Response Relationship Drug Cell Cycle G1 Phase Topotecan/therapeutic use/*toxicity Cell cycle medicine.disease Recombinant Proteins Antineoplastic Agents/therapeutic use/toxicity Oncology chemistry Apoptosis Cell culture Drug Resistance Neoplasm Paclitaxel/therapeutic use/*toxicity Cancer research Topotecan Cell Division medicine.drug |
| Popis: | Malignant gliomas are highly resistant to chemotherapy, in part because of the blood-brain barrier, which restricts the delivery of chemotherapy to certain areas of tumor and their cellular heterogeneity, which leads to the selection and propagation of resistant clones. However, the molecular basis of the drug resistance is poorly understood. In this study, we examined the effect of the cell cycle-inhibitory protein p16 on the chemosensitivity of human glioma cells. Treatment of the p16-null glioma cells, U-251 MG and D-54 MG, with paclitaxel and topotecan, resulted in cell death within 4 days. However, overexpression of exogenous wild-type p16 protein using an adenovirus vector resulted in G1 arrest of glioma cells and resistance to the anticancer effect of paclitaxel or topotecan. Specifically, the p16-expressing cells showed a 30-fold increase in the ID50 of topotecan and a more than 40-fold increase in the ID50 of paclitaxel. These observations indicate that overexpression of molecules that control cell-cycle progression may be partially responsible for causing the resistance of glioma cells to cytocidal drugs. Int J Oncol |
| Databáze: | OpenAIRE |
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