The interleukin-6 signal transducer glycoprotein 130 (gp130) is a co-receptor for cytokines of the interleukin (IL)-6 family and heavily N-glycosylated. While gp130 is expressed ubiquitously the IL-6 receptor is present only in hepatocytes, leukocytes, but also in cancer cells. In particular, circulating IL-6 levels are elevated in late stage melanoma patients and have unfavourable prognosis. We have recently shown that the cholesterol lowering drugs, the statins trigger apoptosis in metastatic melanoma cells, while radial growing melanoma cells are virtually insensitive (Minichsdorfer et al., 2015) to statin induced apoptosis. Moreover, statins affect the glycosylation machinery in the endoplasmic reticulum by a reduction of dolichol, but it is unclear whether a statin like simvastatin alters the glycosylation status of gp130 and impairs IL-6 signalling in human melanoma cells in a stage dependent manner. Experiments were carried out with various human melanoma cells lines reflecting early radial growth phase (WM35) and advances metastatic stages (WM793b, A375 and A518a2) of the disease. The melanoma cells were analysed for cell surface expression of the IL-6 receptor and gp130 by FACS and confirmed by Western blot, including STAT3 and phosphorylated STAT3. IL-6 levels were determined with ELISA, qPCR and activation of STAT3 was monitored by a luciferase reporter assay. Treatments were analysed with ANOVA and post hoc Dunnett test for statistical significance at a p-value of <0.05. The prototypical statin simvastatin induces a concentration and time dependent induction of the glycoprotein gp130. Upon incubation times longer than 24 hours accelerate migration of gp130 in SDS-PAGE, shifting the 130 kDa band to 100 kDa. Interestingly, such a shift is not obtained in WM35 melanoma cells from the early disease stage. Irrespective of the melanoma cell type a deglycosylation pattern is obtained with tunicamycin, an inhibitor of N-linked glycosylation. It is known that deglycosylation of gp130 does not impair IL-6 receptor signalling. IL-6 dependent activation of STAT3 is confirmed by phosphorylation of STAT3, which is also seen with increasing concentrations of simvastatin. Significant activation of the transcription factor STAT3 by already 1 µM simvastatin is further confirmed by a luciferase reporter assay in metastatic melanoma cells. Accordingly, simvastatin treated metastatic melanoma cells secrete significantly more IL-6 into the medium compared to melanoma cells from the early stage. Taken together, our data show that the HMG-CoA reductase inhibitor simvastatin impacts the IL-6 pathway in a stage dependent manner with possible consequences for the tumour microenvirmonment.