人参炔醇重塑巨噬细胞表型调控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

作　　者：邵琦 李佳丽 周李宁 苏兆亮[1] 许化溪[1] SHAO Qi;LI Jia-li;ZHOU Li-ning;SU Zhao-liang;XU Hua-xi(School of Medicine,Jiangsu University,Zhenjiang Jiangsu 212013,China)

机构地区：[1]江苏大学医学院

出　　处：《江苏大学学报（医学版）》2019年第4期287-292,共6页Journal of Jiangsu University：Medicine Edition

基　　金：江苏省社会发展项目(BE2016716);江苏省高校重点实验项目(16KJA320005)

摘　　要：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(0,8,16μg/m L)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0μg/m L组相比,乳腺癌细胞系经8,16μg/m L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16μg/m L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),i NOS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。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 4 T1 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 4 T1 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/m L) 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/m L group,the breast cancer cells proliferation was inhibited by the treatment with 8,16 μg/m L 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/m L),the macrophage phenotype was reversed,the expression of Arg-1 was decreased( P < 0. 01),while the expression of i NOS was increased( P < 0. 01),and the surface antigenpresenting 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.

关 键 词：人参炔醇 巨噬细胞 乳腺癌 极化 肿瘤细胞 细胞增殖 细胞凋亡 

分 类 号：R979.1[医药卫生—药品]