RN1, a novel galectin-3 inhibitor, inhibits pancreatic cancer cell growth in vitro and in vivo via blocking galectin-3 associated signaling pathways
【摘要】：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 up-regulated 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(PDXs). Mechanistically, RN1 binds to epidermal growth factor receptor(EGFR) and Gal-3, thereby disrupting the interaction between Gal-3 and EGFR and down-regulating 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.
【作者单位】：Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences State Key Laboratory of Natural Medicines, China Pharmaceutical University Department of General Surgery, Changzheng Hospital, Second Military Medical University
RN1, a novel galectin-3 inhibitor, inhibits pancreatic cancer cell growth in vitro and in vivo via blocking galectin-3 associated signaling pathways@Lei Zhang$Glycochemistry Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sci