Effect Of Cross-talking Between The JAK/STAT3 And TGF-?1 Signaling Pathway On The Progression Of Hepatocellular Carcinoma Of Rats

Background: Studies showed that aberrant activation of Janus protein tyrosinekinase(JAK)/signal transducer and activator of transcription 3(STAT3)signaling pathway promoted the development of hepatocellular carcinoma(HCC).Transforming growth factor-?1(TGF-?1)has dual-direction regulation effect on the development of various tumors.Objective: To investigate the effect of specifically blocking the JAK/STAT3 signaling pathway on the development of hepatocellular carcinoma and on the expression of TGF-?1.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 16 th week,all rats were sacrificed.The maximum diameter of hepatic tumor nodules was recorded and the maximum diameter greater than 1 cm were counted.Expression and distribution of STAT3 and TGF-?1 in liver tissue were determined by real-time PCR,immunohistochemistry,and immunofluorescence.Results: Compared with the control group,expressions of STAT3 and TGF-?1 m RNA were significantly increased in HCC group(P<0.05).Phosphorylated STAT3(p-STAT3)and TGF-?1 proteins were absent in liver tissue in control group,and both up-regulated and co-expressed in HCC group.While in HCC+AG490 group,expressions of STAT3 and TGF-?1 m RNA were significantly lower than those in HCC group(P<0.05);the liver tissue was weakly positive for p-STAT3 and TGF-?1 proteins,and the number of tumor nodules and its maximum diameter were markedly reduced when compared with the HCC group[1.20±1.03 and(1.14±0.18)cm vs.4.30±1.06and(1.78±0.27)cm,P all<0.05].Conclusion: JAK/STAT3 signaling pathway probably has a synergistic effect with TGF-?1 signaling on the progression of HCC of rats.Specific inhibition of JAK/STAT3 signaling pathway may restrain the tumorigenesis and progression of HCC partially by interfering TGF-?1 signaling pathway.