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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Apoptosis, Blotting, Western, Carcinoma, Hepatocellular, Cell Line, Tumor, Cell Proliferation, Cell Survival, Deferoxamine, Drug Synergism, Flow Cytometry, Humans, Interferon-gamma, Liver Neoplasms, Receptors, Interferon, STAT1 Transcription Factor.
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Does deferoxamine enhance anti-proliferative effect of interferon-gamma against hepatocellular carcinoma cells? Context: Interferon-gamma (IFN-gamma) is a multifunctional cytokine, whose anti-proliferative effect is expected to be of therapeutic value against human cancer. However, hepatocellular carcinoma (HCC) shows resistance to the anti-proliferative effect of IFN-gamma, due mainly to down-regulation of IFN-gamma receptor chain 2 (IFN-gammaR2), even though IFN-gamma receptor chain 1 (IFN-gammaR1), the domain that includes the binding site of IFN-gamma, is stably expressed. The aims of this study were to investigate whether iron chelation, blocking of the human insulin-like growth factor-1 receptor (hIGF1R), or both could upregulate IFN-gammaR2 and enhance the anti-proliferative effect of IFN-gamma. Two HCC cell lines, HuH7 and SNU449, were treated with the iron-chelating agent deferoxamine (DFO), IFN-gamma, and/or anti-hIGF1R blocking antibody. The expression of IFN-gammaR1 and IFN-gammaR2 was then evaluated by flow cytometry and Western blotting. The anti-proliferative effect of IFN-gamma was investigated by MTT assay, and the pro-apoptotic effect was investigated by annexin-V flow cytometry. DFO and blocking with anti-hIGF1R antibody increased the expression of IFN-gammaR2, but the effect on IFN-gammaR1 expression was less marked. DFO, anti-hIGF1R blocking antibody, or both directly enhanced the anti-proliferative effect of IFN-gamma through increased pro-apoptotic activity.
assistant
The present results indicate that IFN-gamma reinforced by iron modulation could be a promising new therapeutic approach for HCC. Final Decision: yes