Abstract
Transcatheter arterial chemoembolization (TACE) is one of the effective treatment methods for hepatocellular carcinoma (HCC) in middle and late phases. However, TACE-induced hypoxia may promote the angiogenesis and section of some cytokines, such as IL-8, and, thereby, lead to tumor metastasis. Therefore, we investigated the effect of Jiedu Recipe (JR), which has been demonstrated as an effective Traditional Chinese Medicine (TCM) recipe on HCC, on TACE-induced cytokines upregulation and hypoxia-induced angiogenesis. A total of 88 hepatocellular carcinoma (HCC) patients treated with TACE were enrolled and divided into a JR group or control group. TACE induced significant increases of neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), IL-1β, IL-2R, IL-6, and IL-8. JR treatment significantly inhibited the elevation of IL-8 compared with control. In vitro, JR significantly inhibited the hypoxia-induced overexpression of IL-8, HIF-1α, and VEGF mRNA in Huh 7 cells. ELISA assay demonstrated the effect of JR on IL-8 expression. Both hypoxia and IL-8 may promote angiogenesis which was suppressed by JR. Western blot showed that IL-8 upregulated the expression of phosphorylation of AKT, ERK, NF-κB, and VEGFR, which were inhibited by JR. On the other hand, effects of IL-8 on the increase of p-AKT and p-ERK were also blocked by LY294002 and U0126, respectively. In conclusion, our results indicated that JR may inhibit hypoxia-induced angiogenesis through suppressing IL-8/HIF-1α/PI3K and MAPK/ERK pathways after TACE in HCC patients.