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Oxyresveratrol prevents murine H22 hepatocellular carcinoma growth and lymph node metastasis via inhibiting tumor angiogenesis and lymphangiogenesis

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Abstract

The purpose of this study was to investigate the effects and mechanisms of oxyresveratrol (Oxyres) on hepatocellular carcinoma (HCC) in vitro and in vivo. The MTT and Transwell assays were performed to investigate the effects of Oxyres on cell proliferation and migration of two HCC cell lines, QGY-7701 and SMMC-7721 cells. H22 cells were subcutaneously injected into hind foot pads of 70 male mice to establish a lymph node metastasis model. These mice were randomly divided into seven groups as follows, control group, HCC group, Oxyres 20 mg/kg group, Oxyres 40 mg/kg group, Oxyres 60 mg/kg group, Resveratrol (Res) group, and Adriamycin (ADM) group. Oxyres, Res, and ADM were intraperitoneally injected daily for consecutive 21 days. Tumors and popliteal lymph node were isolated and embedded for histology analysis. Expressions of CD31 and vascular endothelial growth factor receptor-3 (VEGFR3) in tumors were detected by immunohistocehmistry. Expressions of vascular endothelial growth factor C (VEGF-C) were measured by Western blot. Oxyres significantly inhibited the proliferation and migration of QGY-7701 and SMMC-7721 cells. Oxyres significantly inhibited tumor growth (p < 0.001) and metastasis to sentinel lymph nodes (70%) in a dose-dependent manner. Oxyres showed a similar inhibition rate as Res. Oxyres also significantly decreased micro-blood vessel density and micro-lymphatic vessel density in tumors (p < 0.05). Expressions of CD31, VEGFR3, and VEGF-C of tumors were also inhibited by Oxyres (p < 0.05). Oxyres exerts anti-tumor effects against HCC through inhibiting both angiogenesis and lymph node metastasis, which suggests Oxyres be a potential therapeutic agent.

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Acknowledgements

We sincerely thank Dr. Yu Yu of the Research Laboratory of Pharmaceutical Chemistry and Biomaterials, Chongqing University of Medical Science for kindly giving us QGY-7701 cells.

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  1. Yuanqi Liu and Wei Ren contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, 3-17 Renmin South Road, Chengdu, 610041, Sichuan, People’s Republic of China

    Yuanqi Liu, Wei Ren, Yang Bai, Lihong Wan, Xiaodong Sun, Yin Liu, Wenbi Xiong, Yuan-Yuan Zhang & Liming Zhou

  2. Institute of Laboratory Animals, Sichuan Academy of Medical Sciences and Sichuan Provincial Peolpe’s Hospital, Chengdu, Sichuan, People’s Republic of China

    Wei Ren

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  1. Yuanqi Liu
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The study was approved by the Ethics Committee of Sichuan University, Chengdu, China with the reference number: K2016040.

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Liu, Y., Ren, W., Bai, Y. et al. Oxyresveratrol prevents murine H22 hepatocellular carcinoma growth and lymph node metastasis via inhibiting tumor angiogenesis and lymphangiogenesis. J Nat Med 72, 481–492 (2018). https://doi.org/10.1007/s11418-018-1173-2

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