The Protective and Immunomodulatory Effects of Fucoidan Against 7,12-Dimethyl benz[a]anthracene-Induced Experimental Mammary Carcinogenesis Through the PD1/PDL1 Signaling Pathway in Rats

• Published in: Nutrition and cancer 2017-11, Vol.69 (8), p.1234-1244
• Main Authors: Xue, Meilan, Liang, Hui, Tang, Qingjuan, Xue, Chuanxing, He, Xinjia, Zhang, Li, Zhang, Zheng, Liang, Zhengyan, Bian, Kang, Zhang, Lichen, Li, Zhuxin
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; AKT protein; Algae; Animal tissues; Anthracene; Apoptosis; Blood; Body weight; Cancer; Carcinogenesis; Carcinogens; CD3 antigen; CD4 antigen; CD8 antigen; Cell death; Diet; Flow cytometry; Foxp3 protein; Fucoidan; Immunomodulation; Immunoregulation; Interferon; Interleukin 10; Interleukin 12; Lymphocytes; Lymphocytes T; PD-1 protein; Rats; Rodents; Signal transduction; Signaling; Transforming growth factor-b; Tumors
• ISSN: 0163-5581; 1532-7914
• DOI: 10.1080/01635581.2017.1362446

Fucoidan is a sulfated polysaccharide that is extracted from brown algae seaweed. This study was designed to evaluate the protective and immunomodulatory effects of dietary fucoidan on 7,12-dimethyl benz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Sixty Sprague-Dawley rats were randomly assigned to four equal groups: the control group (control group), the cancer model group (model group), and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg/kg·body weight, respectively. We found that fucoidan treatment decreased the tumor incidence and mean tumor weight and prolonged the tumor latency. Flow cytometric analyses revealed that the number of blood natural killer cells was higher after fucoidan treatment and that the proportions of CD4 and CD8 T cells were also increased. The serum levels of interleukin (IL)-6, IL-12p40, and interferon (IFN)-γ were higher in the rats treated with fucoidan compared to those of model rats. Moreover, the percentage of CD3+ Foxp3+ regulatory T cells in the blood and the levels of IL-10 and transforming growth factor β in the serum were lower in the rats treated with fucoidan. Furthermore, fucoidan treatment decreased the expression of Foxp3 and programmed cell death 1 ligand 1 (PDL1) in tumor tissues. The levels of p-phosphatidyl inositol kinase 3 and p-AKT in tumor tissues were also lower than those of model rats. These results suggest that a fucoidan-supplemented diet can inhibit DMBA-induced tumors in rats. This study provides experimental evidence toward elucidating the immune enhancement induced by fucoidan through the programmed cell death 1/PDL1 signaling pathway. The immunomodulatory effect is one of the possible mechanisms of the protective effect of fucoidan against mammary carcinogenesis.