曲格列酮对人乳腺癌MDA-MB-231和MCF-7细胞株增殖影响的研究

Effect of Troglitazone on breast cancer cells MDA-MB-231 and MCF-7

目的:探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂曲格列酮(TRG)对体外培养雌激素受体(ER)阴性乳腺癌MDA-MB-231细胞及ER+乳腺癌MCF-7细胞增殖的影响。方法:以不同浓度的TRG(0～50μmol/mL)分别处理体外培养的MDA-MB-231细胞和MCF-7细胞48h,MTT法检测细胞存活率;流式细胞术(FCM)检测细胞周期分布;蛋白质印迹法检测PPARγ和ER-α的表达。结果:MTT结果示TRG浓度≥5μmol/mL时MDA-MB-231细胞(P值分别为0.006、0.006、0.000和0.000)和MCF-7细胞(P值分别为0.007、0.006、0.004和0.001)的存活率降低。FCM检测结果表明,经TRG作用后肿瘤细胞主要集中在G1期。以上2种检测结果显示,MDA-MB-231细胞对TRG的敏感程度较MCF-7细胞高;蛋白质印迹法检测结果表明,TRG处理后的MDA-MB-231细胞中PPARγ蛋白的表达水平随药物浓度增加逐渐升高(相对强度分别为2.045、2.600和3.038),MCF-7细胞的ER-α表达水平则随药物浓度增加逐渐降低(相对强度分别为1.164、1.130和0.680)。结论:TRG对ER+和ER-乳腺癌细胞均有抑制作用,且ER-乳腺癌细胞对TRG更敏感。

OBJECTIVE： To investigate the effect of Peroxisomc proliferator activated receptorY （PPARY） agonist Troglitazone （TRG） on estrogen receptor alpha （ER-a） positively expressed breast neoplasms MDA-MB-231 cells and negatively expressed MCF-7 cells. METHODS： The MDA-MB-231 and MCF-7 cells were treated by TRG in different concentrations （0 50 μmol/mL） for 48 hours. MTT method was used to test the survival rate of the cells; Flow cytome try technique test （FCM） for the dis＇fribution of the cancer cell cycle and Western blot for the expression of PPAR）＇ and ER-a. RESULTS： The survival rates of the MDA-MB-231 cells （P wdues were 0. 006,0. 006,0. 000 and 0. 000） and MCF 7 cells （P values were 0. 007,0. 006,0. 004 and 0. 001） treated with TRG in high concentration （≥5 μmol/mL） were decreased. The FCM test results indicated that the tumor cells treated by TRG mainly concentrated in the G1 phase. The MDA MB231 cells showed higher sensitivity to TRG than to MCF-7 cells. The Western blot showed that the ex- pression level of PPAR y in the MDA-MB 231 cells was increased （relative intensity was 2.045,2. 600,3. 038） .and ER-a in the MCF-7 cells were decreased （relative intensity was 1. 164,1. 130.0. 680）. CONCLUSION： Both theER＋ and ER-- breast neoplasms ceils can be inhibited by TRG and the ER-- breast neoplasms cells are more sensitive to TRG.