米非司酮对子宫内膜癌细胞株HHUA裸鼠移植瘤生长及survivin、caspase-3的影响

Effect of mifepristone on the expressions of survivin and caspase-3 in the xenograft of endometrial carcinoma HHUA

目的:研究米非司酮(mifeprisitone,MIF)对子宫内膜癌细胞系HHUA裸鼠移植瘤生长的抑制作用及对survivin、caspase-3的影响。方法:体外培养子宫内膜癌HHUA细胞接种裸鼠皮下建立裸鼠移植瘤动物模型,随机将20只移植瘤荷瘤裸鼠分为两组,分别用MIF、精制花生油治疗6周。观察治疗前后移植瘤体积的变化。HE染色观察肿瘤组织的病理变化。免疫组织化学染色法检测移植瘤组织survivin表达,Image-proplus 4．1．00软件分析系统进行染色结果半定量分析,应用RT-PCR方法检测肿瘤组织survivin、caspase-3的mRNA表达,并用Alphalmager 2200系统进行分析。结果:MIF组移植瘤体积115．25±10．97mm^3,对照组移植瘤体积313．25±43．92mm^3,二者差异有统计学意义(P＜0．01);HE染色示MIF组移植瘤坏死面积较对照组显著增加;MIF组survivin HSCOREs为85．9±11．2,对照组207．6±39．6,两者差异有统计学意义(P＜0．01);MIF组survivin mRNA光密度比值为1．65±0．17,对照组2．75±0．23,两者差异有统计学意义(P＜0．01);MIF组caspase-3的mRNA光密度比值为3．98±0．32,对照组2．12±0．25,两者差异有统计学意义(P＜0．01)。结论:MIF具有抑制子宫内膜癌裸鼠移植瘤生长的作用;其机制可能与下调survivin、上调caspase-3表达有关。

Objective：To investigate the inhibitory effect of antiprogestins mifepristone on the xenograft of nude mice of endometrial carcinoma cell line HHUA and the influence of survivin, caspase-3. Method ：Twenty nude mice with xenograft of endometrial carcinoma HHUA were divided randomly into two groups, namely, the mifepristone group and control group. The nude mice of mifepristone group were fed with the close of mifeprisotne 50mg · kg^-1 ·d^-1 , and the nude mice of control group were fed with peanut oil for 6 weeks, respectively. The growth and sizes of xenograft were measured before and after the treatment. The changes of xenograft morphology were observed by light microscopy with HE staining. The intensity and the distribution of survivin expression were analyzed by an Image-proplus 4.1.00 immunohistochemical scoring system. The survivin and caspase-3 mRNA expressions were measured by RT-PCR and analyzed by Alphalmager 2200. Result： After 6 weeks of treatment, the size of the xenografts of mifepristone group was 115.25 ± 10.97 mm^3 ,which was lower than the 313.25±^43.92mm3 of control group（P 〈0.01 ）. The xenograft of mifepristone group showed significant necrosis motphology changes.The survivin HSCORE of mifeprisotne group was 85.9±11.2,which was lower than the 207.6±39.6 of control group（P〈0.01）,and survivin-mRNA levels of mifeprisotne group was 1.65±0.17,which was lower than 2.75±0.23 of control group（p〈0.01）.The caspase-3-mRNA levels of mifepristone group was 3.98±0.32,which was higher than the 2.12±0.25 of control group（P〈0.01）.Conclusion：Mifepristone significantly inhibits the growth of the xenografts of endometrial carcinoma HHUA in nude mice by down-regulating the expression of survivin and up-regulating the expression of caspase-3.