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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

A small molecular agent YL529 inhibits VEGF-D-induced lymphangiogenesis and metastasis in preclinical tumor models in addition to its known antitumor activities

Authors: Youzhi Xu, Wenjie Lu, Peng Yang, Wen Peng, Chunting Wang, Manli Li, Yan Li, Guobo Li, Nana Meng, Hongjun Lin, Lixin Kan, Siying Wang, Shengyong Yang, Luoting Yu, YingLan Zhao

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

The lymph node metastasis is a key early step of the tumor metastatic process. VEGFD-mediated tumor lymphangiogenesis plays a key role, since down-regulation of p-VEGFR-3 could block the lymph node metastasis. YL529 has been reported to possess potent anti-angiogenesis and antitumor activities; however, its roles in tumor-associated lymphangiogenesis and lymphatic metastasis remain unclear.

Method

We investigated the effect of YL529 on tumor-associated lymphangiogenesis and lymph node metastasis using in vitro lymph node metastasis models and in vivo subcutaneous tumor models in C57 BL/6 mice.

Result

We found that YL529 inhibited VEGF-D-induced survival, proliferation and tube-formation of Human Lymphatic Endothelial Cells. Furthermore, in established in vitro and in vivo lymph node metastasis models using VEGF-D-LL/2 cells, YL529 significantly inhibited the tumor-associated lymphangiogenesis and metastasis. At molecular level, YL529 down-regulated p-VEGFR-3, p-JNK and Bax while up-regulated Bcl-2.

Conclusion

YL529 provided the therapeutic benefits by both direct effects on tumor cells and inhibiting lymphangiogenesis and metastasis via the VEGFR-3 signaling pathway, which may have significant direct clinical implications.
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Metadata
Title
A small molecular agent YL529 inhibits VEGF-D-induced lymphangiogenesis and metastasis in preclinical tumor models in addition to its known antitumor activities
Authors
Youzhi Xu
Wenjie Lu
Peng Yang
Wen Peng
Chunting Wang
Manli Li
Yan Li
Guobo Li
Nana Meng
Hongjun Lin
Lixin Kan
Siying Wang
Shengyong Yang
Luoting Yu
YingLan Zhao
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1451-2

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