Basic fibroblast growth factor potentiates cisplatinum-induced cytotoxicity in MCF-7 human breast cancer cells
| Autor: | Jardena Nordenberg, Joachim Yahalom, Lina Wasserman, T. Livnat, G. Lilling, Robert Wieder, Eyal Fenig, Einat Beery, S. Sharkon-Polak |
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| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
Basic fibroblast growth factor Antineoplastic Agents Apoptosis Breast Neoplasms Cell Separation Biology chemistry.chemical_compound medicine Tumor Cells Cultured Humans RNA Neoplasm Cytotoxicity Cisplatin Cell growth Reverse Transcriptase Polymerase Chain Reaction Drug Synergism General Medicine DNA Neoplasm Flow Cytometry Microscopy Electron Oncology chemistry MCF-7 Proto-Oncogene Proteins c-bcl-2 Cancer cell Cancer research DNA fragmentation Female Fibroblast Growth Factor 2 medicine.drug |
| Zdroj: | Journal of cancer research and clinical oncology. 125(10) |
| ISSN: | 0171-5216 |
| Popis: | Basic fibroblast growth factor (bFGF) is a classical mitogen in fibroblasts and endothelial cells. Our previous studies have demonstrated that bFGF inhibits the growth of MCF-7 human breast cancer cells. The aim of the present study was to examine the effect of bFGF on cis-diamminedichloroplatinum(cisplatin)-induced cytotoxicity in MCF-7 breast cancer cells as compared to normal endothelial cells. MCF-7/NCF cells transduced with a vector expressing the bFGF gene and overexpressing its product, and MCF-7/N2 cells transduced with the backbone vector were incubated with a combination of bFGF and cisplatin for 5 days; results were compared with those obtained with bovine aortic endothelial cells. Cell proliferation was assessed with the sulforhodamine B colorimetric cytotoxicity assay. Apoptosis was quantitatively determined by flow-cytometric analysis for DNA damage and the apoptotic death assay for DNA fragmentation, and qualitatively by electron microscopy. Reverse transcriptase/polymerase chain reaction analysis and an enzyme immunoassay were used to determine the mRNA and protein level, respectively, of the anti-apoptotic bcl-2 gene product. We found that bFGF enhanced cisplatin-induced cytotoxicity in MCF-7 breast cancer sublines. bFGF enhanced proliferation of normal endothelial cells and did not increase cisplatin-induced cytotoxicity. This effect was accompanied by down-regulation of the anti-apoptotic protooncogene bcl-2 and the enhancement of cisplatin-induced apoptosis. We suggest that the improved understanding of the role of bFGF in the differential modulation of the response of breast cancer and normal endothelial cells to chemotherapy may enable active intervention to alter the therapeutic ratio favorably in breast cancer patients. |
| Databáze: | OpenAIRE |
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