RN1, a novel galectin-3 inhibitor, inhibits pancreatic cancer cell growth in vitro and in vivo via blocking galectin-3 associated signaling pathways
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- 英文论文题名：RN1, a novel galectin-3 inhibitor, inhibits pancreatic cancer cell growth in vitro and in vivo via blocking galectin-3 associated signaling pathways
- 论文作者：Lei Zhang ; Peipei Wang ; Yi Qin ; Qifei Cong ; Chenghao Shao ; Zhenyun Du ; Xinyan Ni ; Ping Li ; Kan Ding
- 英文论文作者：Lei Zhang ; Peipei Wang ; Yi Qin ; Qifei Cong ; Chenghao Shao ; Zhenyun Du ; Xinyan Ni ; Ping Li ; Kan Ding ; 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
- 年：2016
- 作者机构：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;
- 英文论文关键词：RN1 ; galectin-3 ; pancreatic cancer ; inhibitor ; Runx1
- 会议召开时间：2016-10-20
- 会议录名称：中国化学会·2016全国多糖研讨会论文摘要集
- 英文会议录名称：Proceedings of 2016 China Polysaccharide Conference
- 语种：英文
- 分类号：R285
- 学会代码：ZGHY
- 会议名称：中国化学会·2016全国多糖研讨会
- 会议地点：中国上海
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：165k
- 原文格式：D
- 会议级别：全国
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.
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.
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.
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