替勃龙对去势裸鼠子宫内膜癌移植瘤的影响

The influence of tibolone on endometrial carcinoma xenografts in ovariectomized nude mice

目的通过裸鼠子宫内膜癌移植瘤模型的体内实验,探讨替勃龙应用于子宫内膜癌患者的安全性。方法 (1)体外培养人子宫内膜癌Ishikawa细胞株;建立去势裸鼠子宫内膜癌Ishikawa细胞株皮下移植瘤动物实验模型;(2)将成瘤裸鼠随机分为替勃龙组(15只)和对照组(15只),分别予以替勃龙0.375mg·kg-1·d-1和对照治疗35d;(3)比较给药前后两组肿瘤体积变化、肿瘤重量和肿瘤转移状况(体表、盆腹腔淋巴结、腹水);应用免疫组化SP法测定两组实验动物皮下移植瘤Ki67、P53、P27、bcl-2蛋白表达情况,判断替勃龙对移植瘤的影响和对内膜癌细胞增殖及凋亡的影响。结果 (1)替勃龙组和对照组裸鼠两组子宫内膜癌皮下移植瘤体积变化无统计学差异[(2.063±1.038)cm3vs.(2.170±0.822)cm3,P=0.791];肿瘤重量无统计学差异[(0.699±2.02)gvs.(0.807±2.83)g,P=0.314];替勃龙治疗35d后,没有引起子宫内膜癌肿瘤体表、盆腹腔转移和腹水发生;(2)替勃龙组和对照组两组裸鼠人子宫内膜癌Ishikawa细胞株皮下移植瘤Ki67增殖指数、P53、P27、bcl-2蛋白表达情况均无统计学差异。结论替勃龙不刺激裸鼠子宫内膜癌Ishikawa细胞株皮下移植瘤生长、转移和细胞增殖、凋亡。替勃龙应用于子宫内膜癌患者的术后激素补充治疗可具有一定的安全性。

Objective To investigate the safety of Tibolone in endometrial carcinoma patients through endometrial carcinoma xenografts model in ovariectomized nude mice in rive. Methods （ 1 ） The test model was established by transplanting subcutaneously the Ishikawa cells,which had been euhured and collected in vitro,into ovariectomized BALB/c nude mice; （2） The nude mice were divided into control and Tibolone group in random, which were fed with placebo or Tibolone （0. 375 mg · kg^-1 · d^-1 ） for 35 days, respectively. The tumor weight, metastasis （abdominopclvie cavity lymph nodes and abdominal dropsy ） and the change of its volume between two groups were compared; （3）Immunochemical SP method was used to determine the expressions of Ki67, P53, P27, bcl- 2 protein in the endometrial carcinoma tissues of the two groups, furthermore, to identify their cell proliferations and apoptosis. Results （ 1 ） No significant differences were observed in the tumor volume enlargement[ （2. 063 ± 1. 038） cm^3 vs. （2. 170 ± 0. 822 ）cm^3,P = 0.791 ] and weight [ （0. 699 -± 2. 02 ） g vs. （ 0. 807 ± 2. 83 ） g, P = 0. 314 ] between Tibolone and control group. 35-day Tibolone usage did not induce tumor metastasis and abdomen fluid development ; （2）No significant differences were tbund in their Ki67 index values, P53, P27 and bcI-2 protein between the two groups. Conclusions Tibolone has no stimulating effects on the growth of Ishikawa endometrial carcinoma cell line xenografts in ovariectomized nude mice. Therefore, its safety could be well guaranteed for endometrial carcinoma patients as hormone replacement therapy.