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Plumbagin Restrains Hepatocellular Carcinoma Angiogenesis by Stromal Cell-Derived Factor (SDF-1)/CXCR4-CXCR7 Axis

Jing Zhong, Junxuan Li, Jiexiao Wei, Delun Huang, Lini Huo, Chuan Zhao, Yuning Lin, Wanjun Chen, Yanfei Wei

Department of Physiology, Faculty of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, China (mainland)

Med Sci Monit 2019; 25:6110-6119

DOI: 10.12659/MSM.915782

Available online:

Published: 2019-08-15

BACKGROUND: Anti-angiogenic therapy has recently emerged as a highly promising therapeutic strategy for treating hepatocellular carcinoma (HCC).
MATERIAL AND METHODS: We assessed cellular proliferation, invasion, and activation of growth factors (VEGF and IL-8) with SDF-1 induced in the hepatocellular carcinoma cell line SMMC-7721, and this progression was limited by plumbagin (PL). The human umbilical vein endothelial cell line HUVEC was co-cultured with SDF-1-induced SMMC-7721, and the expressions of CXCR7, CXCR4, and PI3K/Akt pathways after PL treatment were detected by RT-PCR and Western blot analysis.
RESULTS: The treatment of the hepatoma cell line SMMC-7721 with SDF-1 resulted in enhanced secretion of the angiogenic factors, IL-8 and VEGF, and shows that these stimulatory effects are abolished by PL. The study further demonstrated that PL not only abolishes SDF-1-induced formation of endothelial tubes, but also inhibits expression of CXCR4 and CXCR7, and partially prevents activation of angiogenic signaling pathways.
CONCLUSIONS: The effect of PL on the SDF-1-CXCR4/CXCR7 axis has become an attractive target for inhibiting angiogenesis in hepatoma cells. Our results provide more evidence for the clinical application of PL as part of traditional Chinese medicine in modern cancer treatment.

Keywords: Angiogenesis Inducing Agents, Carcinoma, Hepatocellular, Chemokine CXCL12, Plumbaginaceae, Receptors, CXCR4