Rui Xin, Pan Hua-Feng, Shao Si-Liang, Xu Xiao-Ming
Department of Urology, Ningbo No.2 Hospital, 41 Xibei Street, Ningbo, Zhejiang Province, 315010, China.
BMC Complement Altern Med. 2017 Aug 1;17(1):378. doi: 10.1186/s12906-017-1885-y.
Prostate cancer is the most common cancer in men in the United States. Fucoidan is a bioactive polysaccharide extracted mainly from algae. The aim of this study was to investigate anti-tumor and anti-angiogenic effects of fucoidan in both cell-based assays and mouse xenograft model, as well as to clarify possible role of JAK-STAT3 pathway in the protection.
DU-145 human prostate cancer cells were treated with 100-1000 μg/mL of fucoidan. Cell viability, proliferation, migration and tube formation were studied using MTT, EdU, Transwell and Matrigel assays, respectively. Athymic nude mice were subcutaneously injected with DU-145 cells to induce xenograft model, and treated by oral gavage with 20 mg/kg of fucoidan for 28 days. Tumor volume and weight were recorded. Vascular density in tumor tissue was determined by hemoglobin assay and endothelium biomarker analysis. Protein expression and phosphorylation of JAK and STAT3 were determined by Western blot. Activation of gene promoters was investigated by chromatin Immunoprecipitation.
Fucoidan could dose-dependently inhibit cell viability and proliferation of DU-145 cells. Besides, fucoidan also inhibited cell migration in Transwell and tube formation in Matrigel. In animal study, 28-day treatment of fucoidan significantly hindered the tumor growth and inhibited angiogenesis, with decreased hemoglobin content and reduced mRNA expression of CD31 and CD105 in tumor tissue. Furthermore, phosphorylated JAK and STAT3 in tumor tissue were both reduced after fucoidan treatment, and promoter activation of STAT3-regulated genes, such as VEGF, Bcl-xL and Cyclin D1, was also significantly reduced after treatment.
All these findings provided novel complementary and alternative strategies to treat prostate cancer.
前列腺癌是美国男性中最常见的癌症。岩藻依聚糖是一种主要从藻类中提取的生物活性多糖。本研究的目的是在基于细胞的实验和小鼠异种移植模型中研究岩藻依聚糖的抗肿瘤和抗血管生成作用，并阐明JAK-STAT3信号通路在这种保护作用中可能发挥的作用。
用100 - 1000μg/mL的岩藻依聚糖处理DU-145人前列腺癌细胞。分别使用MTT、EdU、Transwell和基质胶实验研究细胞活力、增殖、迁移和管腔形成。将无胸腺裸鼠皮下注射DU-145细胞以诱导异种移植模型，并用20mg/kg的岩藻依聚糖灌胃处理28天。记录肿瘤体积和重量。通过血红蛋白测定和内皮生物标志物分析确定肿瘤组织中的血管密度。通过蛋白质印迹法测定JAK和STAT3的蛋白表达及磷酸化水平。通过染色质免疫沉淀研究基因启动子的激活情况。
岩藻依聚糖可剂量依赖性地抑制DU-145细胞的活力和增殖。此外，岩藻依聚糖还抑制Transwell实验中的细胞迁移和基质胶实验中的管腔形成。在动物研究中，28天的岩藻依聚糖处理显著阻碍肿瘤生长并抑制血管生成，肿瘤组织中的血红蛋白含量降低，CD31和CD105的mRNA表达减少。此外，岩藻依聚糖处理后肿瘤组织中磷酸化的JAK和STAT3均减少，且处理后STAT3调控基因如VEGF、Bcl-xL和Cyclin D1的启动子激活也显著降低。
所有这些发现为治疗前列腺癌提供了新的补充和替代策略。
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