Journal
CARBOHYDRATE POLYMERS
Volume 204, Issue -, Pages 111-123Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2018.10.008
Keywords
Polysaccharide; Galectin-3; EGFR; FOXO3; Pancreatic ductal adenocarcinoma
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Funding
- Program of Shanghai Subject Chief Scientist [16XD1404500]
- National Natural Science Foundation of China (NSFC) [31670814]
- Shanghai Science and Technology Development Funds [14YF1407800]
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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.
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