Effect of 1α,25(OH)2D3-Treated M1 and M2 Macrophages on Cell Proliferation and Migration Ability in Ovarian Cancer

The biological active form of vitamin D3, 1 alpha,25-dehydroxyvitamin D3 [1 alpha,25(OH)(2)D-3], exerts pleiotropic effects including bone mineralization, anti-tumor, as well as immunomodulator. This study aimed to explore the potential impact of 1 alpha,25(OH)(2)D-3 on tumor-associated macrophages (TAMs) infiltration in ovarian cancer. Firstly, human monocytic THP-1 cells were differentiated into macrophages (M0) in the presence of phorbol 12-myristate 13-acetate (PMA). In Vivo, 1 alpha,25(OH)(2)D-3 not only reversed the polarization of M2 macrophages, but also decreased the proliferation and migration abilities of ovarian cancer cells induced by M2 macrophages supernatant. Furthermore, 1 alpha,25(OH)(2)D-3 dramatically decreased the secretion of TGF-beta 1 and MMP-9 in M2 macrophages. However, no significant effect was observed in 1 alpha,25(OH)(2)D-3 treated M1 macrophages. In Vivo, vitamin D3 had an inhibitive effect of 1 alpha,25(OH)(2)D-3-treated M2 macrophages on tumorigenesis. In addition, we conducted the association of TAMs with the poor prognosis of patients with ovarian cancer by meta-analysis, which suggested the higher proportion of M2 macrophages was related to the poorer prognosis in ovarian cancer. Collectively, these results identified distinct roles of 1 alpha,25(OH)(2)D-3 treated M1 and M2 macrophages on cell proliferation and migration abilities in ovarian cancer.

Automated summary

The study revealed that 1 alpha,25(OH)(2)D-3 has inhibitory effects on the growth and migration abilities of cancer cells, can reverse the polarization of M2 macrophages, and reduce the secretion of TGF-beta 1 and MMP-9 in TAMs. Additionally, the higher proportion of M2 macrophages was associated with poorer prognosis in ovarian cancer patients.