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[地西他滨对裸鼠移植人子宫内膜癌作用的研究。]

[The Study of Decitabine Effect on the Endometrial Carcinoma Xenografted in Nude Mice.].

作者信息

Li Ran-Hong, Wang Xue-Ping, Liu Hui

机构信息

Department of Obstetrics and Gynecology,West China Second University Hospital,Sichuan University,Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University),Ministry of Education,Chengdu 610041,China.

Department of Obstetrics and Gynecology,the People's Hospital of Deyang City,Deyang 618000,China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2016 Nov;47(6):843-847.

Abstract

OBJECTIVES

To explore the effect of the demethylation drug 5-Aza-CdR on endometrial carcinoma xenografted in nude mice.

METHODS

Randomly assigned the mice into decitabine (AZA),cisplatin (DDP),medroxyprogesterone acetate (MPA),AZA+DDP,AZA+MPA,DDP+MPA and model groups (three in each group) after building the models of xenografted tumor by transplanting the HEC-1B cells on nude mice,and dealt them respectively with corresponding drugs (1 μg/g,single or combination) in the experiment groups and normal saline in model group (injected per 3 d,8 injections in total).Then the tumor inhibitory rates in different groups were calculated.The methylation and protein expression of gene was estimated by methylation specific PCR (MSP) and Western blot respectively,and apoptosis situation of carcinoma cell was estimated by tunel.

RESULTS

Inhibitory rate in AZA+DDP group was the highest,and the lowest was AZA group. gene promoter region methylation levels of AZA,AZA+DDP and AZA+MPA groups significantly reduced and showed obvious demethylation stripes while other groups mainly showed the methylation stripes.The differences of RASSF1A protein expression between AZA,AZA+DDP and AZA+MPA groups were not statistical significant (>0.05),but the three were higher than model group (<0.05);there was no statistically significant difference respectively in the DDP,MPA,DDP+ MPA groups compared with that of model group (>0.05).In the comparison of apoptosis index,model group was the lowest,followed by the three single medicine groups,and the highest was three combination groups (<0.05).

CONCLUSIONS

Demethylation drug 5-Aza-CdR in endometrial cancer treatment has a great potential clinical application value by reversing the abnormal methylation of gene,restoring biological functions of RASSF1A protein and strengthening the efficacy of DDP and MPA.

摘要

目的

探讨去甲基化药物5-氮杂-2'-脱氧胞苷(5-Aza-CdR)对裸鼠移植人子宫内膜癌的作用。

方法

将人子宫内膜癌HEC-1B细胞接种于裸鼠建立移植瘤模型后,随机分为地西他滨(AZA)组、顺铂(DDP)组、醋酸甲羟孕酮(MPA)组、AZA+DDP组、AZA+MPA组、DDP+MPA组和模型组(每组3只),实验组分别给予相应药物(1μg/g,单药或联合用药),模型组给予生理盐水(每3天注射1次,共注射8次)。计算各组肿瘤抑制率。分别采用甲基化特异性PCR(MSP)和蛋白质免疫印迹法检测基因甲基化和蛋白表达,采用TUNEL法检测癌细胞凋亡情况。

结果

AZA+DDP组肿瘤抑制率最高,AZA组最低。AZA组、AZA+DDP组和AZA+MPA组基因启动子区甲基化水平显著降低,出现明显的去甲基化条带,其他组主要表现为甲基化条带。AZA组、AZA+DDP组和AZA+MPA组RASSF蛋白表达差异无统计学意义(>0.05),但均高于模型组(<0.05);DDP组、MPA组、DDP+MPA组与模型组比较差异无统计学意义(>0.05)。凋亡指数比较,模型组最低,其次为3个单药组,最高为3个联合用药组(<0.05)。

结论

去甲基化药物5-Aza-CdR通过逆转基因异常甲基化,恢复RASSF1A蛋白生物学功能,增强DDP和MPA疗效,在子宫内膜癌治疗中具有较大的临床应用潜力。

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