Effect of Specific Inhibition of JAK/STAT3 Signaling Pathway on Hepatocellular Carcinoma in Rats / 胃肠病学

ABSTRACT

Background: Studies showed that aberrant activation of JAK/STAT3 signaling pathway promoted the tumorigenesis and progression of hepatocellular carcinoma (HCC), and transforming growth factor-β1 (TGF-β1) has either tumor-suppressing or tumor-promoting effect in regulation of tumor progression.Aims: To investigate the effect of specific inhibition of JAK/STAT3 signaling pathway on HCC and whether TGF-β1 signaling pathway is involved in this process or not.Methods: Thirty Wistar rats were randomly divided into three groups: control group, HCC group, and HCC+AG490 group.In the latter two groups, diethylnitrosamine was administered in drinking water to induce HCC model, and in HCC+AG490 group, AG490, a specific inhibitor of JAK was injected intraperitoneally in the first week of model establishment.At the end of the 16th week, all rats were sacrificed.The maximum diameter of tumor nodules in the liver was recorded and the number of tumors with maximum diameter greater than 1 cm was counted.Expression and distribution of STAT3 and TGF-β1 in liver tissue were determined by real-time PCR, immunohistochemistry, and immunofluorescence.Results: Compared with the control group, expressions of STAT3 and TGF-β1 mRNA in liver tissue were significantly increased in HCC group (P<0.05).Phosphorylated STAT3 (p-STAT3) and TGF-β1 proteins were absent in liver tissue in control group, and both were up-regulated and co-expressed in HCC group.While in HCC+AG490 group, expressions of STAT3 and TGF-β1 mRNA were significantly lower than those in HCC group (P<0.05);the liver tissue was weakly positive for p-STAT3 and TGF-β1 proteins, and the number of tumor nodules greater than 1 cm and the maximum diameter were markedly reduced when compared with the HCC group [1.20±1.03 and (1.14±0.18) cm vs.4.30±1.06 and (1.78±0.27) cm, P all<0.05].Conclusions: Specific inhibition of JAK/STAT3 signaling pathway may restrain the tumorigenesis and progression of HCC partially by interfering TGF-β1 signaling pathway.