Xiaotan Sanjie decoction inhibits angiogenesis in gastric cancer through Interleukin-8−linked regulation of the vascular endothelial growth factor pathway

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Jun Shi, Ye Lu, Pinkang Wei
Ethnopharmacological relevanceInterleukin-8 (IL-8) as a pro-angiogenic factor is strongly associated with gastric cancer metastasis. Xiaotan Sanjie (XTSJ) decoction is an empirical compound prescription based on the phlegm theory of traditional Chinese medicine. Previous studies have shown that XTSJ decoction decreases IL-8 level and formation of vasculogenic mimicry of gastric cancer.Aim of the studyTo investigate the link between Xiaotan Sanjie (XTSJ) decoction and IL-8 regulation in the angiogenesis of gastric cancer.Materials and methodsHuman umbilical vein endothelial cells (HUVECs) were co-cultured with SGC-7901 human gastric cancer cells and exposed to serum samples containing XTSJ decoction and/or IL-8 (1.0ng/mL). The canalization and migration capacities were evaluated by tube formation and transwell migration assay. Protein (immunofluorescence and Western blot) and mRNA (qPCR) expressions were measured in 24-h–cultured HUVECs for vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor receptor (VEGFR)-1, and VEGFR-2.ResultsIL-8 significantly promoted and XTSJ decoction inhibited HUVEC tube formation and migration. Links between IL-8 regulation and XTSJ decoction were found in tube formation and migration assays. IL-8 upregulated and XTSJ decoction downregulated VEGF-A, VEGFR-1, and VEGFR-2 protein levels. XTSJ decoction inhibited IL-8-induced VEGF-A and VEGFR-1 protein expressions. Similarly, IL-8 promoted VEGF-A, VEGFR-1, and VEGFR-2 mRNA levels; however, XTSJ decoction inhibited only VEGF-A mRNA. Interestingly, XTSJ decoction inhibited IL-8−induced VEGFR-1 and VEGFR-2 mRNA expression.ConclusionXTSJ decoction might inhibit angiogenesis in gastric cancer through IL-8-linked regulation of the VEGF pathway.

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