Inhibiting IL-6/STAT3/HIF-1α signaling pathway suppressed the growth of infantile hemangioma
Abstract Purpose This study aimed to evaluate the expression of Interleukin 6 (IL-6) in IH patients and investigate the role of IL-6/signal transducers and activators of transduction-3 (STAT3)/hypoxia inducible factor-1α (HIF-1α) pathway in the progression of infantile hemangioma (IH). Methods Serum samples obtained from IH patients and normal infants were measured for IL-6 expression. Hemangioma-derived stem cells (HemSCs) were transfected with siRNAs targeting IL-6, HIF-1α or STAT3. And then, cell-viability assay and wound healing assay were conducted. After that, the tumor mouse model of HemSCs was established. The in vivo anticancer effect of IL-6 inhibitor was investigated. Results IH patients had much higher IL-6 levels as comparing to the healthy controls (P=0.005). HemSCs transfected with IL-6 siRNA had significantly lower viability and migration rate than normal HemSCs. And HemSCs transfected with STAT3 siRNA or HIF-1α siRNA had the similar tendency. On tumor bearing mice, IL-6 inhibitor treatment significantly delayed the tumor growth. Compared with control group, Caspase 3 was significantly increased in IL-6 inhibitor group (P<0.05), whereas Ki67 was decreased in IL-6 inhibitor group (P<0.05). In TUNEL assay, IL-6 inhibitor group had much higher apoptosis rate than control (P<0.05). Conclusion Our findings indicated that inhibiting IL-6/STAT3/HIF-1α signaling pathway could suppress IH growth.