VPA、SAHA和DAC对子宫内膜癌细胞系抑制作用的研究  

Effect of VPA,SAHA and DAC on Endometrial Carcinoma Cell Lines

作　　者：郭晶 陈星[2] 伊铁忠[3] 吴迪[3] 郑建华[3] 

机构地区：[1]齐齐哈尔建华医院,黑龙江齐齐哈尔161003 [2]浙江省台州医院,浙江台州317000 [3]哈尔滨医科大学附属第一医院,黑龙江哈尔滨150001

出　　处：《实用妇产科杂志》2012年第7期546-551,共6页Journal of Practical Obstetrics and Gynecology

基　　金：黑龙江省青年科学技术专项资金项目(编号:QC07C99);黑龙江省教育厅科学技术研究面上项目(编号:11531133)

摘　　要：目的:观察丙戊酸(VPA)、软木酰苯胺氧肟酸(SAHA)和5-氮-2-脱氧胞苷(DAC)对子宫内膜癌细胞RL-952和HEC-1-B的增殖抑制作用,及对细胞周期、凋亡情况和上皮型钙黏素(E-cad)基因表达的影响。方法:以VPA、SAHA和DAC作用于子宫内膜癌细胞,应用噻唑蓝(MTT)比色法、流式细胞仪和透射电镜对细胞增殖、周期和凋亡情况进行观察。应用逆转录-聚合酶链反应(RT-PCR)法观察药物作用后细胞内E-cadmRNA表达的情况。结果:VPA、SAHA和DAC作用HEC-1-B和RL-952细胞,随着药物浓度的增加,增殖抑制率明显增加(6.77%～93.25%和3.24%～89.25%,5.61%～97.36%和2.56%～87.85%,8.25%～92.54%和5.56%～93.47%)(P<0.01);同一浓度药物随着作用时间的延长(24～96小时)对HEC-1-B和RL-952细胞增殖抑制率明显增加(42.41%～82.74%和36.17%～71.05%,43.15%～82.09%和40.38%～85.93%,43.26%～91.44%和37.75%～85.37%)(P<0.01)。HEC-1-B和RL-952细胞G0/G1期所占比例,经VPA、SAHA、DAC作用24小时后均较对照组增高,差异有高度统计学意义(P<0.01)。应用VPA、SAHA和DAC后细胞凋亡发生率均较对照组增高,差异有高度统计学意义(P<0.01),出现特征性凋亡形态特征。VPA、SAHA和DAC作用后,RL-952和HEC-1-B细胞E-cadmRNA表达上调,较对照组均增加,差异有统计学意义(P<0.05)。结论:VPA、SAHA和DAC可有效抑制子宫内膜癌RL-952和HEC-1-B细胞增殖,有明显的细胞周期阻滞和诱导凋亡作用,对E-cad基因具有明显上调作用。Objective： To observe the changes of cell cycle,apoptosis and E-cad mRNA expression in RL-952 and HEC-1-B endometrial carcinoma cell lines treated with VPA , SAHA and DAC. Methods： RL-952 and HEC-1-B cells were cultured in the presence of VPA, SAHA and DAC. The cellular proliferation inhibitory ratio was evaluated by M＇l-r assay and E-cad mRNA expression was detected by RT-PCR. Flow cytometry （FCM） was used to monitor the cell cycle arrest and apoptosis, Transmission electronic micro- scope（TEM） was applied to observe the apoptosis cellular morphology. Results： With increased concentra- tion and extended culture time, the inhibitory rates of tumor cell growth were notably increased by VPA, SA- HA and DAC （6.77% - 93.25%/3.24% - 89.25%/5.56% - 93.47% and 5.61% - 97.36%/2.56% - 87.85%/8.25% -92.54%, respectively） （ P 〈 0.01 ）. The inhibitory rates of tumor cells were 42.41% - 82.74%/36.17% -71.05% ,43.15% -82.09%/40.38% -85.93% and 37.75% -85.37%/43.26% - 91.44% with the extended culture time（24 -96 h）. VPA ,SAHA and DAC can enhance the ratio of G 0/G1in cell cycle（ P 〈0.01 ）, and can induce tumor cell apoptosis （ P 〈 0.01 ）. The expression of E-cad mRNA was higher in cells cultured in VPA ,SAHA and DAC than that in control group （P〈0.05）. Conclusions： VPA, SAHA and DAC can upregulate E-cad mRNA expression,inhibit the growth and induce the apoptosis of endometrial carcinoma cells.

关 键 词：子宫内膜癌 丙戊酸 软木酰苯胺氧肟酸 5-氮-2-脱氧胞苷 上皮型钙黏素 

分 类 号：R737.33[医药卫生—肿瘤]