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

Abstract

The biological active form of vitamin D3, 1α,25-dehydroxyvitamin D3 [1α,25(OH)₂D₃], exerts pleiotropic effects including bone mineralization, anti-tumor, as well as immunomodulator. This study aimed to explore the potential impact of 1α,25(OH)₂D₃ 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, 1α,25(OH)₂D₃ 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, 1α,25(OH)₂D₃ dramatically decreased the secretion of TGF-β1 and MMP-9 in M2 macrophages. However, no significant effect was observed in 1α,25(OH)₂D₃ treated M1 macrophages. In Vivo, vitamin D3 had an inhibitive effect of 1α,25(OH)₂D₃-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 1α,25(OH)₂D₃ treated M1 and M2 macrophages on cell proliferation and migration abilities in ovarian cancer.

Disclosure statement

The authors declare no conflict of interest.

Ethics approval

All procedures and care provided to the animals were approved by the Institutional Animal Care and Use Committee (approval number is ECSU 201800049).

Data availability statement

All data generated or analyzed during this study are included either in this article or in the supplementary materials and methods, figures, and figure legends files.

Additional information

Funding

This study was funded by the National Natural Science Foundation of China (81872622, 81673151, U1832140 and 81703209), and a sub-project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).