MK886对人结肠癌细胞SW480、Caco-2增殖和凋亡的影响

MK886 inhibits cell proliferation and promotes apoptosis in human colon cancer cell lines SW480 and Caco-2

目的:观察5-脂氧合酶活化蛋白(5-lipoxygenase activating protein,FLAP)抑制剂MK886对人结肠癌细胞株SW480、Caco-2增殖和凋亡的影响.方法:噻唑蓝(MTT)比色法检测6.25、12.5、25、50、100、200μmol/L MK886作用24、48、72 h对S W480和C a c o-2细胞的抑制率;A n n e x i n V-F I T C/P I双染流式细胞术检测12.5、25、50、100μmol/L MK886作用72 h的结肠癌细胞凋亡率;流式细胞仪检测12.5、25、50μmol/L MK886作用72 h的结肠癌细胞周期.结果:50μmol/L到200μmol/L的MK886对结肠癌SW480细胞有抑制作用,且存在时效和量效依赖性;而12.5μmol/L到25μmol/L浓度的MK886处理24 h后,对SW480细胞无明显作用,延长时间至48、72 h后,作用有统计学意义,且同样存在时效和量效依赖性;6.25μmol/L的MK886对SW480细胞无抑制作用.25μmol/L到200μmol/L的MK886对结肠癌Caco-2细胞有抑制作用,且存在时效和量效依赖性;而6.25μmol/L到12.5μmol/L浓度的MK886对Caco-2细胞无抑制作用.200μmol/L MK886作用24h即可明显抑制SW480、Caco-2两种结肠癌细胞株的增殖,抑制率接近90%.12.5μmol/L到100μmol/L浓度的MK886对两种结肠癌SW480和Caco-2细胞有凋亡作用,且存在时效和量效依赖性;12.5μmol/L到50μmol/L浓度的MK886可以增加两种结肠癌SW480和Caco-2细胞G0/G1期比例,降低S期比例.结论:MK886具有显著的抑制人结肠癌SW48-0、Caco-2细胞株增殖的作用,该作用可能是通过阻滞细胞于G0/G1期,并诱导肿瘤细胞凋亡所致.

AIM： To observe the effects of 5-lipoxygenaseactivating protein（FLAP） MK886 on cell proliferation and apoptosis in human colon cancer celllines SW480 and Caco-2. METHODS： MTT assay was used to detect theeffects of treatment with MK886 at different concentrations（6.25, 12.5, 25, 50, 100, 200 μmol/L）for different durations（24, 48, 72 h） on the proliferation of SW480 and Caco-2 cells. The apoptosis of cells treated with MK886 at concentrations of 12.5, 25, 50, and 100 μmol/L for 72 h was assessed by flow cytometry with annexin V-FITC/ PI. The cell cycle of cells treated with MK886 at concentrations of 12.5, 25, and 50 μmol/L for 72 h was assessed by flow cytometry. RESULTS： MK886 at concentrations between 50 and 200 μmol/L inhibited the proliferation of SW480 cells in a dose- and time-dependent manner. Treatment with MK886 at concentrations from 12.5 to 25 μmol/L for 24 h did not significantly inhibit the proliferation of SW480 cells, but treatment for 48 h or 72 h significantly inhibit cell proliferation in a dose- and timedependent manner. MK886 at a concentration of 6.25 μmol/L had no significant effects on the proliferation of SW480 cells. In Caco-2 cells, MK886 at concentrations from 25 to 200 μmol/L inhibited cell proliferation in a dose- and time-dependent manner, but MK886 at concentrations between 6.25 and 12.5 μmol/L MK886 had no significant inhibitory effect on the proliferation of Caco-2 cells. Treatment with MK886 at a concentration of 200 μmol/L for 24 h significantly inhibited the growth of SW480 and Caco-2 cells, and the reduced rate of cell growth was 90%. MK886 at concentrations from 12.5 to 100 μmol/L increased the apoptosis rate of the two cell lines in a dose- and time-dependent manner. Treatment with MK886 at concentrations from 12.5 to 50 μmol/L for 72 h increased the percentage of cells in G0/G1 phase but decreased that in S phase. CONCLUSION： MK886 significantly inhibits the growth of SW480 and Caco-2 cells possibly by blocking cells in G0/G1 phase and inducing cell apoptosis.