Title |
A small molecular agent YL529 inhibits VEGF-D-induced lymphangiogenesis and metastasis in preclinical tumor models in addition to its known antitumor activities
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Published in |
BMC Cancer, July 2015
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DOI | 10.1186/s12885-015-1451-2 |
Pubmed ID | |
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 |
Abstract |
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. 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. 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. 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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Scientists | 1 | 33% |
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Other | 1 | 8% |
Student > Bachelor | 1 | 8% |
Professor | 1 | 8% |
Student > Ph. D. Student | 1 | 8% |
Other | 2 | 17% |
Unknown | 4 | 33% |
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Unknown | 4 | 33% |