Preventive effects of microvesicles isolated from Bifidobacterium bifidum on 4T1-induced breast cancer in BALB/c mice

Introduction: Breast cancer is one of the important causes of mortality among women. Many studies have focused on the development of natural health products for prevention and treatment of breast cancer. This study investigated the effects of Bifidobacterium bifidum and its microvesicles (MVs) on 4T1-induced breast cancer in BALB/c mice. Methods: Sixty female BALB/c mice were divided into 5 groups: (1) negative control, (2) positive control, (3) doxorubicin, (4) probiotic and (5) MVs (isolated from B. bifidum). The mice in groups 4 and 5 were pretreated with B. bifidum and MVs for 4 weeks, respectively. Tumor was induced by subcutaneous administration of 4T1 cell culture. After tumor development, mice in group 3 were treated with doxorubicin while other groups were treated as before. The mice were sacrificed after 3 weeks, breast tumors were removed and histologically examined. Also, P53 and Ki67 protein were evaluated by immunohistochemistry staining, and P53 gene expression was assessed by RT-PCR. Results: Pretreatment with MVs and probiotic reduced mortality and tumor growth rate. MVs and Probiotic prevented the weight loss and suppressed tumor cell proliferation which was indicated by Ki-67 and p53. The expression of p53 confirmed these results. Despite the malignancy in the breast tissue, necrosis of cancer cells occurred in the mice treated with MVs. Conclusion: MVs of B. bifidum effectively inhibited breast cancer development in mice and suppressed tumor cell proliferation. Probiotic microorganisms and their metabolites can be used as a functional food to prevent breast cancer.