Increased expression of IL-6 mRNA in hepatocellular carcinoma cell lines correlates with biological characteristics.

Background & aims: IL-6 has been implicated in both virus-associated and diethylnitrosamine-induced hepatocellular carcinomas (HCCs). Generally it is produced by immune cells such as Kupffer cells inthe liver. To understand mechanisms by which IL-6 might participate in the genesis of HCCs, the production of IL-6 by cell lines under different conditions was examined to determine inducing factors Methods: Expression of IL-6 mRNA in both hepatoma cell lines and a normal liver cell line L-02 was measured by quantitative RT-PCR. Biological molecules including liposome, dsRNA and cell debris were used to stimulate IL-6 mRNA expression in HepG2 cells and inhibition was effected by RNAi. Proliferation was assessed by MTT and clone formation and migration was determined by scratch assay. Results: All of the HCC cell lines observed expressed IL-6 mRNA, including HepG2, Bel-7402(7402), MHCC-97H and SMMC-7721. Normal liver cell line L-02 also expressed IL-6 mRNA. SiRNA to IL-6 specifically knockdowned IL-6 mRNA expression in HepG2, and liposome, dsRNA and cell debris increased it. Both proliferation and migration of HepG2 cells were related to the level of IL-6 HepG2 expressed. Conclusion: Both normal liver cell line and HCC cell lines can produce IL-6 so that Kupffer cells are noit the only source of the cytokine in the liver well as other immune cells. That the fact that HCC cells reacted to stimulation of biological molecules such as liposome, dsRNA or cell debris with increasing production of IL-6 indicates that the cytokine might play an important role not only in the period of tumor initiation but progression and recurrence as well.