Background/aims: The receptor of interferon-gamma (IFN-gammaR) consists of IFN-gammaR1 and R2. Resistance to the anti-proliferative effect of IFN-gamma is due to downregulation of IFN-gammaR2. The aim of this study was to investigate whether iron chelation could upregulate IFN-gammaR2 and enhance the anti-proliferative effect of IFN-gamma in colon cancer cell lines.
Methodology: The colon cancer cell lines, SW480, COLO, and WiDr were treated with the iron chelating agent DFO, and the expression of IFN-gammaR1 and IFN-gammaR2 was evaluated by FACS. The anti-proliferative effect of IFN-gamma was investigated by MTT assay, and the proapoptotic effect was investigated by FACS with Annexin-V.
Results: FACS demonstrated that DFO increased the expression of IFN-gammaR2, whereas the effect on IFN-gammaR1 expression was less marked. MTT assay showed that cell growth was inhibited by DFO. Addition of DFO and IFN-gamma inhibited further, but inhibition was not observed with IFN-gamma alone. Apoptotic cells were increased by DFO, and further increased with DFO + IFN-gamma together.
Conclusions: Expression of IFN-gammaR2 is restored by iron chelation, and the increased expression of IFN-gammaR2 enhances the anti-proliferative effect of IFN-gamma through induction of apoptosis in colon cancer cells.