米非司酮对乳腺癌细胞增殖与凋亡的作用机制

目的研究米非司酮（MIF）对乳腺癌细胞增殖抑制以及促进凋亡的机制。方法分别在24、48、72h时观察不同浓度的MIF（1.25、2.50、5.00、10.00、20.00、40.00mg/L）在体外环境下对ER(＋)/ PR(＋)乳腺癌细胞系(MCF-7)生长、凋亡及与之相关的VEGF、bcl-2、Ki67、CerbB-2、p53等因子表达的影响。结果① 空白对照组细胞贴壁均匀，状态良好，各干预组贴壁细胞明显减少，培养液内细胞碎片增多，且随MIF剂量的增加和干预时间的延长效果更趋明显；② 各剂量组四唑盐(MTT)比色试验OD值较空白对照组显著降低(P＜0.01)，且与干预剂量、干预时间成反比，差异有统计学意义(P＜0.01)；③ 与空白对照组相比，各干预组早期凋亡细胞所占比例显著增加(P＜0.01),各剂量组间差异有统计学意义(P＜0.01)；④ 免疫组织化学检测各组ER、PR表达无明显差异，而VEGF、bcl-2、Ki67、CerbB-2、p53表达10.00、20.00mg/L组与2.50、5.00mg/L组比较，差异有统计学意义(P＜0.01)；⑤ MIF干预后，ER(＋)/PR(＋)细胞各项凋亡指标较干预前有统计学意义(P＜0.01)，细胞活力显著降低。结论① MIF能够抑制ER(＋)/PR(＋)乳腺癌细胞株的生长；② MIF抑制乳腺癌细胞株的生长与促进癌细胞凋亡有关，而且呈时间和剂量依赖性；③ MIF抑制乳腺癌细胞株的生长与其降低相关因子水平及调降微血管生成有关。

Mechanism of mifepristone on proliferation and apoptosis of a breast cancer cell line

To explore the mechanisms of mifepristone on the proliferation and apoptosis of MCF-7 cells in vitro. Methods1.25，2.50，5.00，10.00，20.00 or 40.00mg/L MIF was added into 6 intervention groups and no MIF was added into the control group. Cellular morphological changes were observed under an inverted microscope, the apoptosis rate was measured by a flow cytometer, cell vigor was detected by methyl thiazolyl tetrazolium (MTT), and the expression levels of ER， PR， VEGF， bcl-2， Ki67， CerbB-2 and p53 were determined by immunohistochemistry. Results① Cell adherence was aequalis and in good condition in the control group and decreased in the intervention groups, also cell debris was increased in a dose-and time-dependent manner. ② The optical density significantly degraded in each intervention group(P＜0.01) in a dose- and time-dependent manner by MTT test. ③ The apoptosis rate was much higher in each intervention group than that in the control group (P＜0.01), which was also in a dose- and time-dependent manner(P＜0.01).　④　Expressions of VEGF, bcl-2, Ki67, CerbB-2 and p53 levels were statistically different between the 10.00 and 20.00mg/L groups and the 2.50 and 5.00mg/L groups (P＜0.01), but of ER and PR were not statistically different among each group. ⑤ Every apoptosis index had distinguishing differences and cell vigor had significantly degraded after the interventions(P＜0.01). Conclusions MIF can inhibit the growth of the breast cancer cell possibly by promoting apoptosis in dose- and time- dependent manners and inhibiting proliferation and growth of tumor micro-vessels.