米非司酮对子宫内膜癌HHUA细胞裸小鼠移植瘤生长作用的研究
张秋实;林仲秋;
摘要(Abstract)：
目的探讨米非司酮(RU486)对人子宫内膜癌HHUA细胞裸小鼠移植瘤生长的抑制作用。方法体外培养人子宫内膜癌HHUA细胞,裸小鼠皮下接种HHUA细胞建立裸小鼠移植瘤动物模型,将荷瘤裸小鼠随机分为两组,分别应用米非司酮、精制花生油治疗4周。治疗期间观察各组裸小鼠生长情况、移植瘤体积、增殖率和形态,治疗结束后应用流式细胞术(FCM)检测各组裸小鼠移植瘤组织细胞周期时相的变化和细胞凋亡率;应用免疫组化技术检测基因Bcl-2和Bax蛋白的表达。结果米非司酮组裸小鼠移植瘤体积第3周明显减小,肿瘤增殖率明显降低(P<0.01)。4周治疗结束后米非司酮组裸小鼠移植瘤细胞G0/G1期比例升高(38.17±3.02)%,S期细胞比例(SPF)降低(43.87±4.29)%,与对照组比较差异均有显著性(P<0.05),移植瘤细胞凋亡率为(15.03±2.19)%,明显高于对照组(3.06±1.13)%(P<0.01);治疗组移植瘤细胞Bcl-2蛋白表达明显降低(1.9±0.61),而Bax呈现过度表达(4.0±1.28)(P<0.05)。结论抗孕激素米非司酮(RU486)能显著抑制人子宫内膜癌HHUA细胞裸小鼠移植瘤的生长,其抗肿瘤作用与调控细胞周期时相和诱导细胞凋亡相关。
关键词(KeyWords)： 子宫内膜肿瘤/药物疗法;米非司酮/治疗应用;子宫内膜肿瘤/病理学;细胞周期;细胞凋亡/药物作用
基金项目(Foundation):
作者(Authors): 张秋实;林仲秋;
参考文献(References)：
- [1]Shimizu M,Saitch Y,Itoh H.Immunohistoehemicalstaining of H-ras oncogenic product in normal,benignand malignant human pancreatic tissues[J].HumPathol,1990,21(6):607-612.
- [2]Dardes RC,Schafer JM,Pearce ST,et al.Regulation ofestrogen target genes and growth by selectiveestrogen-receptor modulators in endometrial cancercells[J].Gynecol Oncol,2002,85(3):498-506.
- [3]Schneider CC,Gibb RK,Taylor DD,et al.Inhibition ofendometrial cancer cell lines by mifepristone(RU486)[J].J Soc Gynecol Investig,1998,5(6):334-338.
- [4]富琪,魏丽惠,钱和年,等.米非司酮抗人子宫内膜癌裸小鼠移植瘤作用的实验研究[J].北京医科大学学报,1996,28(4):295-297.
- [5]Runge-Morris M.Regulation of sulfotransferase geneexpression by glucocorticoid hormones and xenobioticsin primary rat hepatocyte culture[J].Chem BiolInteract,1998,109(1-3):315-327.
- [6]Han S,Sidell N.Ru486-induced growth inhibition ofhuman endometrial cell revolves nuclear factor kappaB signaling pathway[J].J Clin Endocrinol Metab,2003,88(2):713-719.
- [7]Bozdogan O,Atasoy P,Erekul S,et al.Apoptosis-related proteins and steroid hormone receptors innormal,hyperplastic,and neoplastic endometrium[J],Int J Gynecol Pathol,2002,21(4):375-382.
- [8]Mora LB,Diaz JI,Cantor AB,et al.Differentialdiagnosis of endometrial hyperplasia and carcinoma bycomputerized image cytometry of cell proliferation,apoptosis and bcl-2 expression[J].Ann Clin Lab Sci,1999,29(4):308-315.
- [9]Tao XJ,Tilly KI,Maravei DV,et al.Differentialexpression of members of the bcl-2 gene family inproliferation and secretory human endometrium:glandular epithelial cell apoptosis is associated withincreased expression of bax[J].J Clin EndocrinolMetab,1997,82(8):2738-2746.