Objective To investigate the effect of Interleukin-4/Interleukin-4 receptor (IL-4/IL-4R) on the biological behavior of hepatocellular carcinoma(HCC) and its underlying mechanism.

Methods Huh7 cells were cultured in vitro and then transfected with small interfering RNAs (siRNAs). Cell proliferation was assessed by CCK8. Cell cycle and apoptosis were analyzed by flow cytometry. The possible signaling proteins were measured by Western blot.

Results The proliferation of Huh7 cells was increased by IL-4 (P=0.01), however the proliferation was suppressed by silencing IL-4R(P=0.00033). After knocking down IL-4R, the early apoptosis of Huh7 cells(P=0.014) and the expression of apoptosis-related proteins Bax(P=0.016), Caspase-3(P=0.029) were enhanced, and the expression of anti-apoptosis-related protein Bcl-2 was decreased(P=0.003). However the late apoptosis rate(P=0.108) and the cell cycle(G₀/G₁ phase, P=0.677; S phase, P=0.139; G₂/M phase, P=0.855) were not changed. Furthermore, IL-4 up-regulated the phosphorylation of JAK1(P=0.01) and STAT6(P=0.005). The phosphorylation levels of JAK1(P=0.016) and STAT6(P=0.019) in Huh7 cells were down-regulated by IL-4R depletion.

Conclusion IL-4/IL-4R can activate JAK1/STAT6 signaling pathway and enhance the proliferation of HCC. Furthermore, IL-4/IL-4R can inhibit the apoptosis of HCC through regulating the expression of apoptotic proteins and anti-apoptotic proteins.