人参炔醇重塑巨噬细胞表型调控乳腺癌细胞生物学行为

目的: 探讨人参炔醇对巨噬细胞表型和功能的调控作用及对乳腺癌细胞生物学行为的影响。方法: 用人参炔醇处理4T1乳腺癌细胞，观察各项生物学行为变化；用4T1乳腺癌细胞培养上清液预处理RAW264.7 巨噬细胞系48 h，诱导其向M2型巨噬细胞极化；极化后的巨噬细胞再分别经不同浓度人参炔醇(0，8，16 μg/mL)处理24 h，用qRT PCR、蛋白质印迹、流式细胞术、ELISA法联合检测各组表型、抗原递呈相关分子MHCⅡ类分子、CD80、CD86表达改变、分泌谱变化，以及细胞系迁移、侵袭等。结果： 与0 μg/mL组相比，乳腺癌细胞系经8，16 μg/mL人参炔醇处理后，细胞增殖率明显降低(P均＜0.01)，细胞凋亡率明显增加(P均＜0.05)，癌细胞趋化作用减弱； M2型巨噬细胞经16 μg/mL人参炔醇刺激后，细胞表型逆转，Arg 1表达明显降低(P均＜0.01)，iNOS表达明显增加(P均＜0.01)，MHCⅡ、CD80、CD86表达升高；并伴随IL 1β、TNF α表达升高(P均＜0.01)，IL 4、IL 8、IL 10表达降低(P均＜0.05)；经人参炔醇处理的巨噬细胞能够明显减少乳腺癌细胞的迁移与侵袭。结论： 人参炔醇可重塑巨噬细胞表型和功能，从而间接改变乳腺癌细胞生物学行为。

Effect of panaxynol on the biological behavior of breast cancer cells by remodeling macrophage phenotype

Objective: To investigate the effects of panaxynol on the phenotype and function of macrophages and the biological behavior of breast cancer cells. Methods: Firstly, breast cancer 4T1 cells were directly treated with panaxynol, and various biological behavior changes were observed. Secondly, the macrophage cell line RAW264.7 was stimulated with breast cancer cell 4T1 culture supernatant for 48 h to induce macrophage polarization to M2 macrophages, and then macrophages were treated with different concentrations of panaxynol(0, 8, 16 μg/mL) for 24 h. qRT PCR, Western blotting, flow cytometry and ELISA were used to detect the phenotypic and antigen presenting related molecules expression changes, such as MHCⅡ, CD80 and CD86, and the secretion spectrum changes, and the influence of panaxynol on the migration and invasion of breast cancer cell lines. Results: Compared with the 0 μg/mL group, the breast cancer cells proliferation was inhibited by the treatment with 8, 16 μg/mL panaxynol(P＜0.01), the cell apoptosis rate was enhanced(P＜0.05), and the chemotaxis of cancer cells was weakened. In addition, panaxynol stimulated macrophage showed the M2 phenotype. After stimulation with panaxynol(16 μg/mL), the macrophage phenotype was reversed, the expression of Arg 1 was decreased(P＜0.01), while the expression of iNOS was increased(P＜0.01), and the surface antigen presenting molecules(MHCⅡ, CD80, CD86) was increased significantly, accompanied by the expression level of IL 4, IL 8, IL 10 down regulated(P＜0.01) and IL 1β, TNF α upregulated(all P＜0.05). In addition, panaxynol stimulated macrophages could significantly reduce the number of migrating and invading breast cancer cells. Conclusion: Panaxynol could remodel macrophage phenotype and function, and therefore regulate the biological behavior of breast cancer cells.