Abstract
IL-6 (interleukin 6) plays an important role in the development and growth of hepatocellular carcinoma (HCC) via both classic signaling and trans-signaling pathways. Soluble gp130 (sgp130) is known to be a natural inhibitor of the trans-signaling pathway. In the present study, our goal was to investigate whether recombinant sgp130 could suppress the initiation and progression of HCC in mouse models. Our results demonstrate that sgp130 induced an apoptosis of HepG2 cells and inhibited the clonogenicity of HepG2 in vitro. Moreover, the IL-6 trans-signaling pathway is significantly suppressed by sgp130 as reflected by the decrease in the level of STAT3 phosphorylation and other inflammatory factors both in vitro and in vivo. In the DEN-induced HCC mouse model, intravenous injection of sgp130 attenuated hepatic fibrosis at 16 weeks and reduced the initiation and progression of primary HCC at 36 weeks. Furthermore, our results also demonstrate that intravenous administration of sgp130 significantly suppressed the growth and metastasis of xenograft human HCC in NOD/SCID mice.
Highlights
IL-6 plays an important role in the development and growth of hepatocellular carcinoma (HCC) via both classic signaling and trans-signaling pathways
Hepatocellular carcinoma (HCC), which accounts for 80% of primary liver cancers, is associated with inflammation-damaged livers resulting from viral hepatitis infections, or from cirrhosis due to chronic alcoholism[2]
IL-6 modulates the expression of several liver cancer specific genes during the inflammatory state, and autocrine IL-6 is crucial for the initiation and progression of HCC9
Summary
IL-6 (interleukin 6) plays an important role in the development and growth of hepatocellular carcinoma (HCC) via both classic signaling and trans-signaling pathways. Our goal was to investigate whether recombinant sgp[130] could suppress the initiation and progression of HCC in mouse models. The IL-6 trans-signaling pathway is significantly suppressed by sgp[130] as reflected by the decrease in the level of STAT3 phosphorylation and other inflammatory factors both in vitro and in vivo. Our results demonstrate that intravenous administration of sgp[130] significantly suppressed the growth and metastasis of xenograft human HCC in NOD/SCID mice. Our goal was to investigate whether recombinant sgp[130] could effectively suppress the IL-6 trans-signaling pathway and thereby suppress HepG2 cell growth as well as the development of HCC in DEN-treated mice
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