Patients with idiopathic pulmonary fibrosis have a high incidence of lung cancer and a worse prognosis for clinical treatment. A few molecules with antifibrosis properties have been shown promoting cancer progression in clinical trials. The objective of this study was to determine whether there is a similar tendency in mice as in human beings and whether these mice models may be used to find new therapeutic agents with antiflbrotic properties but not cancer-promoting properties. We used bleomycin to induce pulmonary fibrosis in mice with or without naringenin treatment and measured the immune-associated lymphocytes and their secreted cytokines using flow cytometry and ELISA from lung tissue. Both passive and spontaneous metastatic models in bleomycin-treated C57BL/6 and BALB/c mice were used to test the hypothesis that mice with pulmonary fibrosis could have an increased risk of lung cancer and associated cancer progression. Here, we show that mice with lung fibrosis challenged using tumors show an increased incidence of lung metastasis and shorter life spans compared with the mice without lung fibrosis. A fibrotic environment in the lung results in increased abundance of transforming growth factor-ßl and CD4+CD25+Foxp3+ regulatory T cells and a decreased proportion of activated effector T cells. This grave immunosup-pressive environment favors tumor localization and growth. Naringenin significantly reduces lung metastases in mice with pulmonary fibrosis and increases their survival by improving the immunosuppressive environment through down-regulating transforming growth factor-ßl and reducingregulatory T cells. Naringenin could be an ideal therapeutic agent in the treatment of both cancer and fibrosis.
ASJC Scopus subject areas
- Cancer Research