Liposomal honokiol inhibits VEGF-D-induced lymphangiogenesis and metastasis in xenograft tumor model
Correction(s) for this article
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Erratum
- Volume 147Issue 8International Journal of Cancer
- pages: E10-E10
- First Published online: July 15, 2020
Jing Wen
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
The first two authors contributed equally to this work.
Search for more papers by this authorA-fu Fu
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
The first two authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
Li-Juan Chen
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Fax: +86-28-85164060
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Gaopeng Street, Keyuan Street Road 4, Chengdu 610041, Sichuan, ChinaSearch for more papers by this authorXing-Jiang Xie
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorGuang-Li Yang
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorXian-Cheng Chen
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorYong-Sheng Wang
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorJiong Li
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorPing Chen
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorMing-Hai Tang
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorXi Ming Shao
Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorYou Lu
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorXia Zhao
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorYu-Quan Wei
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorJing Wen
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
The first two authors contributed equally to this work.
Search for more papers by this authorA-fu Fu
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
The first two authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
Li-Juan Chen
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Fax: +86-28-85164060
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Gaopeng Street, Keyuan Street Road 4, Chengdu 610041, Sichuan, ChinaSearch for more papers by this authorXing-Jiang Xie
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorGuang-Li Yang
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorXian-Cheng Chen
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorYong-Sheng Wang
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorJiong Li
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorPing Chen
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorMing-Hai Tang
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorXi Ming Shao
Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorYou Lu
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorXia Zhao
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorYu-Quan Wei
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
Search for more papers by this authorAbstract
Lymph nodes metastasis of tumor could be a crucial early step in the metastatic process. Induction of tumor lymphangiogenesis by vascular endothelial growth factor-D may play an important role in promoting tumor metastasis to regional lymph nodes and these processes can be inhibited by inactivation of the VEGFR-3 signaling pathway. Honokiol has been reported to possess potent antiangiogenesis and antitumor properties in several cell lines and xenograft tumor models. However, its role in tumor-associated lymphangiogenesis and lymphatic metastasis remains unclear. Here, we established lymph node metastasis models by injecting overexpressing VEGF-D Lewis lung carcinoma cells into C57BL/6 mice to explore the effect of honokiol on tumor-associated lymphangiogenesis and related lymph node metastasis. The underlying mechanisms were systematically investigated in vitro and in vivo. In in vivo study, liposomal honokiol significantly inhibited the tumor-associated lymphangiogenesis and metastasis in Lewis lung carcinoma model. A remarkable delay of tumor growth and prolonged life span were also observed. In in vitro study, honokiol inhibited VEGF-D-induced survival, proliferation and tube-formation of both human umbilical vein endothelial cells (HUVECs) and lymphatic vascular endothelial cells (HLECs). Western blotting analysis showed that liposomal honokiol-inhibited Akt and MAPK phosphorylation in 2 endothelial cells, and downregulated expressions of VEGFR-2 of human vascular endothelial cells and VEGFR-3 of lymphatic endothelial cells. Thus, we identified for the first time that honokiol provided therapeutic benefit not only by direct effects on tumor cells and antiangiogenesis but also by inhibiting lymphangiogenesis and metastasis via the VEGFR-3 pathway. The present findings may be of importance to investigate the molecular mechanisms underlying the spread of cancer via the lymphatics and explore the therapeutical strategy of honokiol on antilymphangiogenesis and antimetastasis. © 2008 Wiley-Liss, Inc.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
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| IJC_24244_sm_suppfig1.tif165.9 KB | Supplementary Figure 1 |
| IJC_24244_sm_suppfig2.tif841.5 KB | Supplementary Figure 2 |
| IJC_24244_sm_suppfig3.tif1.9 MB | Supplementary Figure 3 |
| IJC_24244_sm_suppfigLeg.doc29.5 KB | Supplementary Figure Legends |
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