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.
Department of General Surgery, Shanghai Changzheng hospital, Second Military Medical University, Shanghai, 200030, China.
Carbohydr Polym. 2019 Jan 15;204:111-123. doi: 10.1016/j.carbpol.2018.10.008. Epub 2018 Oct 5.
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.
胰腺导管腺癌是一种高度恶性的胃肠道肿瘤。胰腺癌的分子靶向治疗仍然有限。在胰腺癌中高表达的半乳糖凝集素-3与疾病进展呈正相关，表明半乳糖凝集素-3可以作为预后不良的预测因子。从红花中我们分离并纯化了一种均一的多糖 HH1-1，它可以与半乳糖凝集素-3结合并抑制其活性。HH1-1 可以阻断半乳糖凝集素-3 与 EGFR 的相互作用。HH1-1 处理后，EGFR 与半乳糖凝集素-3 的结合能力降低了 245.28 倍。HH1-1 可以抑制胰腺癌细胞增殖，将细胞周期阻滞在 S 期，诱导细胞凋亡，抑制血管生成，阻碍肿瘤细胞迁移和侵袭。此外，HH1-1 还影响 Galectin-3/EGFR/AKT/FOXO3 信号通路，并在体外和体内具有抗胰腺癌活性，特别是在患者来源的异种移植模型中。进一步的研究表明，HH1-1 在体外和体内几乎没有毒性。这为 HH1-1 可能成为一种有前途的治疗药物提供了新的证据，并支持将半乳糖凝集素-3 作为胰腺癌治疗靶点的研究。
