HH1-1, a novel Galectin-3 inhibitor, exerts anti-pancreatic cancer activity by blocking Galectin-3/EGFR/AKT/FOXO3 signaling pathway.

Affiliation

Glycochemistry & Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China, University of Chinese Academy of Sciences, No. 19(A) Yuquan Road, Beijing, 100049, China. Electronic address: [Email]

Abstract

Pancreatic ductal adenocarcinoma is a highly malignant gastrointestinal tumor. Molecular targeting therapy for pancreatic cancer is still limited. High expressed Galectin-3 in pancreatic cancer is positively correlated with disease progression, indicating that Galectin-3 can be employed as a predictor of poor prognosis. From safflower, we isolated and purified a homogeneous polysaccharide, HH1-1, which could bind to and inhibit Galectin-3. HH1-1 could block the interaction between Galectin-3 and EGFR. Following HH1-1 treatment, the binding ability between EGFR and Galectin-3 was reduced by 245.28 folds. HH1-1 could suppress pancreatic cancer cell proliferation, arrest the cell cycle in S phase, induce cell apoptosis, inhibit angiogenesis and impede tumor cell migration and invasion. Moreover, HH1-1 affected the Galectin-3/EGFR/AKT/FOXO3 signaling pathway and possessed anti-pancreatic cancer activity in vitro and in vivo, especially in patient-derived xenografts. Further study suggested that HH1-1 had almost no toxicity both in vitro and in vivo. This adds new evidence to suggest that HH1-1 could be a promising therapeutic agent and support the pursuit of the Galectin-3 as a target in pancreatic cancer treatment.

Keywords

EGFR,FOXO3,Galectin-3,Pancreatic ductal adenocarcinoma,Polysaccharide,