期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 19, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ijms19072116
关键词
calcitriol; vitamin D analogs; breast cancer; metastasis; immunosuppression; osteopontin; TGF-beta
资金
- National Science Center [2013/11/B/NZ5/00162]
In our previous study, calcitriol and its analogs PRI-2191 and PRI-2205 stimulated 4T1 mouse mammary gland cancer metastasis. Therefore, we aimed to analyze the inflammatory response in 4T1-bearing mice treated with these compounds. Gene expression analysis of the splenocytes and regional lymph nodes demonstrated prevalence of the T helper lymphocytes (Th2) response with an increased activity of regulatory T (Treg) lymphocytes in mice treated with these compounds. We also observed an increased number of mature granulocytes and B lymphocytes and a decreased number of TCD4(+), TCD4(+) CD25(+), and TCD8(+), as well as natural killer (NK) CD335(+), cells in the blood of mice treated with calcitriol and its analogs. Among the splenocytes, we observed a significant decrease in NK CD335+ cells and an increase in TCD8(+) cells. Calcitriol and its analogs decreased the levels of interleukin (IL)-1 beta and IL-10 and increased the level of interferon gamma (IFN-gamma) in the plasma. In the tumor tissue, they caused an increase in the level of IL-10. Gene expression analysis of lung tissue demonstrated an increased level of osteopontin (Spp1) and transforming growth factor beta (TGF-beta) mRNA. The expression of Spp1 was also elevated in lymph nodes. Calcitriol and its analogs caused prevalence of tumor-conducive changes in the immune system of 4T1 tumor-bearing mice, despite the induction of some tumor-disadvantageous effects.
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