Influence of silibinin on differential expressions of total cytokine genes in human hepatocellular carcinoma cell lines

Influence of silibinin (0.3, 1 μg/mL) on expressions of total cytokine genes in two human hepatocellular carcinoma (HCC) cell lines with different characteristics (cell line A, HCC24/KMUH, without susceptible to amphotericin B-induced oxidative stress; cell line B, HCC38/KMUH, susceptible to amphotericin B-induced oxidative stress) was investigated by microarray. 0.3 μg/mL silibinin up-regulated two cytokine genes (IL17D, IL17RB) and down-regulated 13 cytokine genes (CCL2, CCL20, CXCL1, CXCL2, CXCL3, CXCL6, CXCR4, EPO, IL1A, IL1B, IL2RG, IL6, IL8), but 1 μg/mL silibinin only down-regulated four cytokine genes (CCL2, CCL20, CXCL6, IL8) with smaller magnitudes of gene expression fold changes than those caused by 0.3 μg/mL silibinin in cell line B. For genes related to stress, inflammation, hypoxia or reactive oxygen species, 0.3 μg/mL silibinin down-regulated 10 genes (C7orf68, EGLN3, PDZK1IP1, SAA1, SAA2, SAA4, SOD2, TFF3, VNN2, VNN3), but 1 μg/mL silibinin only down-regulated two genes (C7orf68, SAA4) with smaller magnitudes of gene expression fold changes than those caused by 0.3 μg/mL silibinin in cell line B. Six genes (CCL2, CCL20, CXCL6, IL6, IL8, SOD2) examined by quantitative reverse transcriptase-polymerase chain reaction had same results with microarray in cell line B, but IL6 in cell line A was up-regulated by 0.3 μg/mL silibinin. In conclusion, the antioxidant effects of silibinin on HCC cells, which may influence the expressions of cytokine genes are determined by the concentration and the characteristics of cancer cells. Down-regulated cytokine genes caused by silibinin in HCC cells susceptible to amphotericin B-induced oxidative stress may have potential to inhibit tumor progression.