Milk fermented by Lactobacillus casei CRL431 administered as an immune adjuvant in models of breast cancer and metastasis under chemotherapy.

Chemotherapy is the most common treatment for breast cancer and its metastasis; however, it affects the patients' quality of life. Previously, it was demonstrated that milk fermented by Lactobacillus casei CRL431 (probiotic fermented milk (PFM)) exerted benefits against breast cancer metastasis by modulating the immune response in a mouse model. The aim of this work was to evaluate PFM administration on the side effects of capecitabine and on its anti-tumour/anti-metastatic effects. In vitro, 4T1 breast cancer cells were treated with capecitabine in the presence of immune cells' conditioned media from mice administered with PFM. Cell viability was evaluated by MTT assay. In vivo, BALB/c mice (healthy, bearing breast cancer or with potential metastasis) were treated or not with capecitabine and administered with PFM. Blood cell counts, intestinal damages, lung histology and serum cytokines were evaluated. Results showed that capecitabine's toxicity on 4T1 cells was improved by the immune cells from mice that received PFM when the lower dose of capecitabine was evaluated. PFM reduced capecitabine side effects in all the mouse models and decreased intestinal mucositis and mortality. PFM administration to mice under chemotherapy maintained the anti-cancer/anti-metastasis effect of capecitabine with similar or decreased values for serum IL-10 and TNF-α and decreased IL-6, a cytokine related to poor prognosis in advanced cancer patients. In addition, PFM by itself reduced metastasis without side effects and improved the host's immune response. PFM has a potential to be administered as an immune adjuvant in patients under chemotherapy without affecting the treatment. KEY POINTS: • Milk fermented by L. casei CRL431 (PFM) diminished capecitabine side effects. • Capecitabine's toxicity on 4T1 cells was improved by the PFM-stimulated immune cells. • PFM maintained anti-cancer/anti-metastasis effect of capecitabine in mouse models. Graphical abstract.