Bleomycin inhibits proliferation and induces apoptosis in TPC-1 cells through reversing M2-macrophages polarization.

Abstract

Papillary thyroid carcinoma (PTC) is one of the most common types of thyroid malignancy. Previous studies have demonstrated that the density of tumor-associated macrophages (TAMs) within the tumor microenvironment affects the progression of PTC due to the imbalance in M1/M2 macrophage subtypes. M2 macrophages induce anti-inflammatory effects and promote tumor progression, whereas M1 macrophages destroy tumor cells. Therefore, reversing TAM polarization to M1 may be a novel strategy for the treatment of cancer. Although bleomycin (BLM) is a commonly used anti-cancer drug, which regulates the secretion of relevant cytokines, high dose and long-term treatment with BLM may lead to pulmonary fibrosis. In the present study, flow cytometry data revealed that low dose treatment with BLM (5 or 10 mU/ml) facilitated the expression of the M1 phenotype markers cluster of differentiation (CD)80 and C-C chemokine receptor 7, and concurrently suppressed the M2 marker CD206 on M2-macrophages. Reverse transcription-quantitative polymerase chain reaction data revealed that the expression levels of tumor necrosis factor-α and interleukin-1β markedly increased, whereas the expression of IL-10 decreased in M2 macrophages treated with BLM. A fluorescein isothiocyanate-dextran uptake experiment revealed that BLM increased the phagocytic capacity of M2, however not M1 or M0 macrophages. In addition, to verify the effect of BLM-treated M2 macrophages on thyroid carcinoma cells, a co-culture system of macrophages and the human PTC cell line TPC-1, was established. BLM-treated M2 macrophages increased the number of cells in early and late apoptosis and inhibited the migration, proliferation and invasion of TPC-1 cells. These results suggest that a low dose and indirect effect of BLM may induce suppressive effects on PTC by selectively reversing M2 macrophage polarization to M1, which may provide a novel strategy for cancer treatment.