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岩藻依聚糖促进乳腺癌细胞凋亡并抑制其上皮-间质转化

Fucoidan Promotes Apoptosis and Inhibits EMT of Breast Cancer Cells.

作者信息

He Xinjia, Xue Meilan, Jiang Shu, Li Weiwei, Yu Jinming, Xiang Shuai

机构信息

School of Medicine, Shandong University.

Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences.

出版信息

Biol Pharm Bull. 2019;42(3):442-447. doi: 10.1248/bpb.b18-00777.

DOI:10.1248/bpb.b18-00777
PMID:30828076
Abstract

Fucoidan is an active component of seaweed, and could inhibit proliferation and induce apoptotic cell death in several tumor cells. However, the function of fucoidan in breast cancer is largely unknown. In the present study, we evaluated the anti-cancer potential of fucoidan in human breast cancer MCF-7 cells. Adult Sprague-Dawley rats were randomized to receive fucoidan (200 or 400 mg/kg·body weight per day) or normal saline via gastric gavage for 3 consecutive days. Serum samples were prepared from these rats, and used for subsequent experiments to examine the potential effects in MCF-7 cells. Cell viability was determined using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was examined with Hoechst33258 staining and flow cytometry. Cell migration and invasion were measured by wound scratch assay and Transwell assay, respectively. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to examine the expression of secretory E-cadherin and matrix metalloproteinase-9 (MMP-9). Conditioned serum from fucoidan-treated rats significantly suppressed cell proliferation and enhanced apoptosis. Cell migration and invasion were also significantly decreased. Observed effects of conditioned serum were associated with upregulation of E-cadherin and downregulation of MMP-9. Conditioned serum of rats treated with fucoidan could inhibit the proliferation and promote apoptosis of MCF-7 cells. Cell invasion and migration were inhibited, possibly via decreased epithelial-mesenchymal transition (EMT) process. Fucoidan may be a promising therapeutic agent for human breast cancers.

摘要

岩藻依聚糖是海藻的一种活性成分,能够抑制多种肿瘤细胞的增殖并诱导其凋亡性细胞死亡。然而,岩藻依聚糖在乳腺癌中的作用在很大程度上尚不清楚。在本研究中,我们评估了岩藻依聚糖对人乳腺癌MCF-7细胞的抗癌潜力。将成年Sprague-Dawley大鼠随机分为两组,连续3天经口灌胃给予岩藻依聚糖(200或400mg/kg体重)或生理盐水。从这些大鼠制备血清样本,并用于后续实验以检测对MCF-7细胞的潜在影响。使用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四唑溴盐(MTT)法测定细胞活力。通过Hoechst33258染色和流式细胞术检测细胞凋亡。分别采用伤口划痕试验和Transwell试验测量细胞迁移和侵袭能力。使用蛋白质免疫印迹法和酶联免疫吸附测定(ELISA)检测分泌型E-钙黏蛋白和基质金属蛋白酶-9(MMP-9)的表达。岩藻依聚糖处理大鼠的条件血清显著抑制细胞增殖并增强细胞凋亡。细胞迁移和侵袭也显著降低。观察到的条件血清作用与E-钙黏蛋白上调和MMP-9下调有关。岩藻依聚糖处理大鼠的条件血清可抑制MCF-7细胞的增殖并促进其凋亡。细胞侵袭和迁移受到抑制,可能是通过减少上皮-间质转化(EMT)过程实现的。岩藻依聚糖可能是一种有前景的人类乳腺癌治疗药物。

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