Abstract
Background. It is known that immunologic factors are involved in the regulation of the growth of ovarian carcinoma and that granulocytes are often found on the site of ovarian cancer. Therefore, we chose to investigate the effects of cytokines on UT-OC-2 ovarian endometrioid adenocarcinoma cells in vitro. In order to investigate the molecular mechanisms involved, the activation of two key DNA-binding proteins, AP-1 and transcription factor NF-κB (NF-κB), was studied. Since DNA extracted from the UT-OC-2 cells showed fragmentation typical of apoptosis, we also studied the effects of cytokines on this event. Methods. The effects of the studied cytokines on the proliferation of UT-OC-2 cells were investigated by 125I-deoxyuridine incorporation. The activation of DNA-binding proteins was studied by electrophoretic mobility shift assay. Statistical analyses were performed by Student's t-test. Results. Interferon α (IFN-α), transforming growth factor β1 (TGF-β1), tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) all had a significant inhibitory effect on cell proliferation. Granulocyte colony stimulating factor (GM-CSF) did not alter cell proliferation significantly. Transcription factors AP-1 and NF-κB were both found to be constitutively active in UT-OC-2 ovarian carcinoma cells. We were able to show that IFN-γ, TGF-β1 and TNF-α all increased the binding activity of transcription factor AP-1 (AP-1). The binding activity of transcription factor NF-κB was not altered by any of the cytokines studied, with the exception of IFN-γ. IFN-γ had also a clear inhibitory effect on the apparent magnitude of apoptosis, whereas TNF-α and TGF-β1 showed no effect. Conclusion. The results of this study show that TNF-α, TGF-β1, and IFN-γ are able to inhibit the proliferation of UT-OC-2 ovarian carcinoma cells. Activation of AP-1 seems to be involved in the growth-regulating processes induced by IFN-γ, TGF-β1 and TNF-α; IFN-γ is also able to increase the binding activity of NF-κB and inhibited apoptosis in ovarian cancer cells.
| Abbreviations | ||
| GM-CSF | = | granulocyte colony stimulating factor |
| IFN-α | = | interferon α |
| IFN-γ | = | interferon γ |
| TGF-β1 | = | transforming growth factor β1 |
| TNF-α | = | tumor necrosis factor α |
| AP-1 | = | transcription factor AP-1 |
| NF-κB | = | transcription factor NF-κB |
| Abbreviations | ||
| GM-CSF | = | granulocyte colony stimulating factor |
| IFN-α | = | interferon α |
| IFN-γ | = | interferon γ |
| TGF-β1 | = | transforming growth factor β1 |
| TNF-α | = | tumor necrosis factor α |
| AP-1 | = | transcription factor AP-1 |
| NF-κB | = | transcription factor NF-κB |