Anti-metastatic Efficacy of Traditional Chinese Medicine (TCM) Ginsenoside Conjugated to a VEFGR-3 Antibody on Human Gastric Cancer in an Orthotopic Mouse Model.
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| Abstract |
Background/Aim: The aim of the present study was to investigate the efficacy of a traditional Chinese medicine (TCM), VEGFR-3 antibody-conjugated ginsenoside Rg 3 nanoemulsion (VRIN), targeting lymphangiogenesis, on the inhibition of tumor growth and metastasis in an orthotopic mouse model of human gastric cancer. Materials and Methods: An orthotopic nude-mouse model of gastric cancer was established with the red fluorescent protein (RFP)-expressing human gastric cancer cell line NUGC-4-RFP. The tumor-bearing mice were treated with vehicle (0.2 ml normal saline every other day, iv), 5-FU (20 mg/kg once a week, i.p.) and VRIN (1 mg/kg every other day, i.v.). Real-time fluorescence imaging was performed to assess tumor inhibition in each group. Metastasis was evaluated by open fluorescence imaging at autopsy. The expression of lymphangiogenesis-related factors VEGF-C, VEDF-D and VEGFR-3 in the tumors were analyzed by immunohistochemistry and real-time RCP. Results: VRIN and 5-FU significantly inhibited primary tumor growth as compared to vehicle control (p<0.05). However, significant inhibition of lymph-node metastasis was only found in the VRIN-treated group (p<0.05). The expression of VEGF-C, VEGF-D and VEGFR-3 in the tumor was suppressed by VRIN treatment (p<0.05). Expression of VEGF-D and VEGFR-3 in the 5-FU-treated group was not significantly increased (p>0.05). No obvious toxicity was found in VRIN- and 5-FU-treated groups. Conclusion: Lymphangiogenesis-targeted ginsenoside Rg 3 immune-nanoemulsion inhibited tumor growth and reduced lymphatic metastasis by suppressing expression of VEGF-C, VEGF-D and VEGFR-3 in an orthotopic mouse model of human gastric cancer. Our study demonstrates the potential of TCM as an effective targeted treatment for metastatic gastric cancer.
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| Authors | Xiaojun Dai, Dongmei Liu, Moxiang Liu, Xiaochun Zhang, Weiming Wang, Feng Jin, Yayun Qian, Xuanyi Wang, Jingjing Zhao, Yongjian Wu, Fangfang Xiong, N A Chang, Y U Sun, Zhijian Yang, Robert M Hoffman, Yanqing Liu |
| Journal | Anticancer research (Anticancer Res) Vol. 37 Issue 3 Pg. 979-986 (03 2017) ISSN: 1791-7530 [Electronic] Greece |
| PMID | 28314255 (Publication Type: Journal Article) |
| Copyright | Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. |
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