PPARs在子宫内膜腺癌细胞中的表达及其激动剂对子宫内膜癌细胞生长抑制的影响

PPARs expression and anticancer role of rosiglitazone in endometrial cancer.

目的:探讨过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors,PPARs)在子宫内膜癌细胞中的表达及PPARγ激动剂罗格列酮(Rosiglitazone)对体外培养人子宫内膜癌细胞系HHUA、KLE生长抑制和凋亡的影响。方法:RT-PCR检测PPARs在子宫内膜癌细胞中的表达;用MTT比色法分别检测罗格列酮作用于子宫内膜癌细胞HHUA、KLE不同时间后的细胞生长抑制率;流式细胞仪分析细胞周期分布; TUNEL检测细胞凋亡。结果:RT-PCR结果显示,两种子宫内膜癌细胞中均有PPARαPPARγmRNA表达,未见到PPARβmRNA表达;罗格列酮对人子宫内膜癌细胞的生长有抑制作用,呈时间剂量依赖性;流式细胞仪(FCM)检测结果显示盐酸罗格列酮作用于人子宫内膜癌细胞24h后,细胞周期被阻滞于G_1期;荧光显微镜,TUNEL检测显示, 200μmol/L罗格列酮作用子宫内膜癌细胞24h后出现典型的凋亡现象,细胞凋亡率为(18．3±1．9)%,与对照组(2．66±0．49)%相比差异有统计学意义(P＜0．05)。结论:罗格列酮对人子宫内膜癌细胞系的生长具有明显的抑制作用,促进细胞凋亡,其抗肿瘤作用机制可能是通过活化PPARγ途径诱导了细胞凋亡。

Objective：To investigate the expression of peroxisome proliferator-activated receptors（PPARs） and the selective effect of rosiglitazone on growth and apoptosis in endometrial cancer cell line cultured in vitro. Methods：PPARs mRNA expression was detected by reverse transcriptase polymerase chain reaction. Cell proliferation was measured by MTF colorimetric assay. Cell cycle percentage were detected by flow cytometry. Apoptotic cells were detected by the methods of TUNEL assay. Results：PPARα and PPARγmRNA expression was detected in HHUA, KLE cells. Rosiglitazone significantly inhibited endometrial cell growth in a dosedependent manner and a time-dependent manner. After treatment with rosiglitazone,the cell cycle arrested at G1 phase and the S phase fraction decreased. Endometrial cancer cells showed typical apoptosis changes after PPARγactivation. The apoptosis rate was （ 18.3 ± 1.9 ） % after treatment with 200μmol/L Rosiglitazone for 24 hours. The difference was significant compared with that of the control （2.66 ± 0.49 ） % （ P 〈 0.05 ）. Conclusion ： Our findings suggested that rosiglitazone can inhibit the proliferation of endometrial carcinoma cell in vitro, its anticancer effect seems to be due to induction of apoptosis which may be a result of up-regulating PPARγ.