Chao Zhang1,2, Qingrui Li1,3, Guozheng Qin4, Yi Zhang1, Chaoying Li5, Liwen Han6, Rongchun Wang7, Shudan Wang5, Haixia Chen8, Kechun Liu9, Chengwei He10. 1. Beijing University of Chinese Medicine, Beijing, 100102, China. 2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China. 3. Aerospace Central Hospital, Beijing, 100049, China. 4. Yunnan Provincial Hospital of Traditional Chinese Medicine/The First Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, 650021, China. 5. School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China. 6. Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250062, China. 7. Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China. 8. Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China. 9. Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250103, China. hliukch@sdas.org. 10. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China. chengweihe@umac.mo.
Abstract
BACKGROUND: Polyphyllin VII (PP7), a steroidal saponin from P. polyphylla has been found to exert strong anticancer activity. Little is known about the anti-angiogenesis and anti-metastasis properties of PP7. In this study, the anti-angiogenic and anti-metastatic effects of PP7 on HCC and the molecular mechanisms were evaluated. METHODS: Effect of PP7 on angiogenesis was assessed by tube formation assay and applied a transgenic Tg(fli1:EGFP) zebrafish model. Effects of PP7 on tumor metastasis and invasion were examined in cell migration and invasion assay, zebrafish tumor xenograft models and lung metastasis mouse models. The protein levels were examined by Western blotting. RESULTS: PP7 significantly decreased the tube formation of human umbilical vein endothelial cells, the number and length of ISVs and SIVs of transgenic zebrafish, and the metastasis and invasion of cancer cells in vitro and in vivo. The anti-angiogenic and anti-metastatic effects of PP7 in HepG2 cells were attributable, at least partially, to downregulated NF-κB/MMP-9/VEGF signaling pathway. CONCLUSION: This study demonstrates that PP7 possesses strong anti-angiogenesis and anti-metastasis activities, suggesting that PP7 could be a potential candidate agent for HCC treatment.
BACKGROUND:Polyphyllin VII (PP7), a steroidal saponin from P. polyphylla has been found to exert strong anticancer activity. Little is known about the anti-angiogenesis and anti-metastasis properties of PP7. In this study, the anti-angiogenic and anti-metastatic effects of PP7 on HCC and the molecular mechanisms were evaluated. METHODS: Effect of PP7 on angiogenesis was assessed by tube formation assay and applied a transgenic Tg(fli1:EGFP) zebrafish model. Effects of PP7 on tumor metastasis and invasion were examined in cell migration and invasion assay, zebrafishtumor xenograft models and lung metastasis mouse models. The protein levels were examined by Western blotting. RESULTS:PP7 significantly decreased the tube formation of human umbilical vein endothelial cells, the number and length of ISVs and SIVs of transgenic zebrafish, and the metastasis and invasion of cancer cells in vitro and in vivo. The anti-angiogenic and anti-metastatic effects of PP7 in HepG2 cells were attributable, at least partially, to downregulated NF-κB/MMP-9/VEGF signaling pathway. CONCLUSION: This study demonstrates that PP7 possesses strong anti-angiogenesis and anti-metastasis activities, suggesting that PP7 could be a potential candidate agent for HCC treatment.
Entities:
Keywords:
Anti-angiogenesis; Anti-metastasis; Hepatocellular carcinoma cells; NF-κB/MMP-9/VEGF pathway; Polyphyllin VII
Authors: Qin Jie Wu; Chang Yang Gong; Shun Tao Luo; Dong Mei Zhang; Shuang Zhang; Hua Shan Shi; Lian Lu; Heng Xiu Yan; Sha Sha He; Dan Dan Li; Li Yang; Xia Zhao; Yu Quan Wei Journal: BMC Cancer Date: 2012-03-30 Impact factor: 4.430