期刊
ONCOGENE
卷 36, 期 9, 页码 1297-1308出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2016.306
关键词
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资金
- National Natural Science Foundation of China [31230022]
- New Drug Creation and Manufacturing Program [2012ZX09301001-003]
- National Science Foundation of China [81421005]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA12010302]
Galectin-3 (Gal-3) has been implicated in pancreatic ductal adenocarcinoma (PDAC), and its candidacy as a therapeutic target has been evaluated. Gal-3 is widely upregulated in tumors, and its expression is associated with the development and malignancy of PDAC. In the present study, we demonstrate that a polysaccharide, RN1, purified from the flower of Panax notoginseng binds to Gal-3 and suppresses its expression. In addition, RN1 markedly inhibits PDAC cells growth in vitro, in vivo and in patient-derived xenografts. Mechanistically, RN1 binds to epidermal growth factor receptor (EGFR) and Gal-3, thereby disrupting the interaction between Gal-3 and EGFR and downregulating extracellular-related kinase (ERK) phosphorylation and the transcription factor of Gal-3, Runx1 expression. Inhibiting the expression of Runx1 by RN1, suppresses Gal-3 expression and inactivates Gal-3-associated signaling pathways, including the EGFR/ERK/Runx1, BMP/smad/Id-3 and integrin/FAK/JNK signaling pathways. In addition, RN1 can also bind to bone morphogenetic protein receptors (BMPR1A and BMPR2) and block the interaction between Gal-3 and the BMPRs. Thus, our results suggest that a novel Gal-3 inhibitor RN1 may be a potential candidate for human PDAC treatment via multiple targets and multiple signaling pathways.
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