新型酚类化合物DFTP对结肠癌SW480细胞生物学表型的影响及其机制

Effect and mechanism of DFTP on biological phenotype of colon cancer SW480 cells

目的 探究新型酚类单体化合物2,4-dibromo-3-fluoro-6-(3-(trifluoromethyl) isoxazol-5-yl) phenol (DFTP)对人类恶性肿瘤细胞活性和增殖的抑制作用。方法 选取人结肠癌SW480、肺癌A549以及脑胶质瘤U251细胞系为研究模型,分别用不同浓度的DFTP处理细胞,用CCK-8试剂盒检测细胞活性。选取对DFTP最敏感的结肠癌细胞系SW480为进一步研究对象,用倒置显微镜监测其形态学变化,用细胞划痕实验检测SW480细胞的迁移能力,用EdU荧光染色试剂盒检测SW480细胞的增殖能力,用克隆形成实验检测SW480细胞的克隆形成能力,用流式细胞仪检测SW480细胞的细胞周期,用活细胞/死细胞荧光染色法检测DFTP对SW480的杀伤作用,用Annix-V-FITC细胞凋亡试剂盒检测SW480细胞的凋亡情况。结果 随着DFTP浓度的升高及孵育时间的延长,SW480细胞的迁移能力并未受到显著影响(F=1.849,P>0.05),但是其细胞形态发生明显变化,细胞活性与细胞周期S期显著降低,细胞的克隆形成能力和增殖能力均受到DFTP的抑制(F=11.897,P<0.001);随着DFTP浓度增加,SW480的细胞死亡现象逐渐显现(F=16.38,P<0.001),经Annix-V-FITC染色实验证实,DFTP能够以浓度依赖性的方式诱导细胞凋亡(F=9.485,P<0.001)。结论 新型酚类单体DFTP对不同肿瘤的癌细胞均有抑制作用,其中对结肠癌细胞最为敏感,DFTP可以通过抑制细胞增殖与诱导细胞凋亡发挥抑制结肠癌细胞的作用。

Objective To investigate the inhibitory effects of 2,4-dibromo-3-fluoro-6-(3-(trifluoromethyl)Isoxazol-5-yl)phenol(DFTP)on the activity and proliferation of human malignant tumor cells.Methods Human colon cancer cell line SW480,lung cancer cell line A549 and brain glioma cell line U251 were selected as research models.The cells were treated with different concentrations of DFTP,and the cell activity was detected by CCK-8 kit.The colon cancer cell line SW480,which was most sensitive to DFTP,was selected as the object for further study.Morphological changes of SW480 cells were monitored by inverted microscope;migration ability of SW480 cells was detected by cell scratching experiment;proliferation ability of SW480 cells was detected by EdU fluorescence staining kit;and colony formation ability of SW480 cells was detected by colony formation assay.The cell cycle of SW480 cells was detected by flow cytometry,the killing effect of DFTP on SW480 cells was detected by live cell/dead cell fluorescence staining,and the apoptosis of SW480 cells was detected by Annix-V-FITC apoptosis kit.Results With the increase of DFTP concentration and the extension of incubation time,the migration ability of SW480 cells was not significantly affected,but the cell morphology was significantly changed,cell activity and cell cycle S phase were significantly reduced,and the colony formation ability and proliferation ability of SW480 cells were inhibited by DFTP.Moreover,as DFTP concentration increased,cell death of SW480 gradually appeared.Annix-V-FITC staining result confirmed that DFTP could induce cell apoptosis in a concentration-dependent manner.Conclusion The new phenolic monomer-DFTP has an inhibitory effect on cancer cells of different tumors,especially colon cancer cells.DFTP can inhibit colon cancer cells by inhibiting cell proliferation and inducing cell apoptosis.