【作者】 霍晓溪；

【导师】 刘彦；

【作者基本信息】 第二军医大学 ， 妇产科学， 2008， 博士

【摘要】 目的研究WT1在上皮性卵巢癌组织中的表达及其反义核酸在体内、体外实验中对卵巢癌细胞增殖和凋亡的影响,探讨WT1基因的临床病理学意义和其反义核酸应用于卵巢癌治疗研究的可能性。方法检测各种不同病理类型卵巢组织及经紫杉醇治疗后裸鼠卵巢癌皮下移植瘤组织中WT1和相关凋亡基因的表达,应用WT1反义寡核苷酸转染卵巢癌SKOV₃细胞株,检测、观察转染前后卵巢癌细胞体内、体外增殖和凋亡的改变。结果上皮性卵巢癌、尤其是浆液性囊腺癌组织中WT1的表达明显高于其它组织学类型,且与临床分期、组织学分级相关。经紫杉醇治疗后的裸鼠卵巢癌皮下移植瘤组织中WT1表达下降,同时出现凋亡。WT1反义寡核苷酸转染后的卵巢癌SKOV₃细胞株生长缓慢,早期即发生凋亡,且体外成瘤能力降低。结论WT1在上皮性卵巢癌中高表达,可作为临床诊断的辅助性指标,其生物学效应是通过调节细胞的增殖和凋亡过程来实现的,可能成为卵巢癌治疗新的生物学靶点。更多还原

【Abstract】 Objectives To study the expression of WT1 protein in ovarian carcinoma and the effect of WT1 ASODN inducing proliferation and apoptosis of SKOV₃ in vitro and in vivre.Methods Expression of WT1 and gene correlated with apoptosis were studied in all kinds of ovarian tissues and nude mouse transplanted tumor treated with Taxol. The WT1 ASODN was transferred into SKOV₃ cells.Investigate the changes in expression levels of WT1 protein and cell proliferation and apoptosis in ovarian epithelial after transfection.Results The positive expression rate of WT1 in ovarian epithelial carcinomas,especially in serous carcinomas,was statistically higher than those in other histologic subtypes.There were closed relationship between the expression of WT1 and clinical stage,histological grades,but no relationship with lymph node metastasisand ascites. Low lever of WT1 and apoptosis occurred were detected in nude mice during Taxol treatments.The growth of the ovarian cancer cell lines SKOV₃ transfected by WT1 ASODN became significantly slow and its activity reduced.Apoptosis were found in early stage.The tumorigenic ability of the SKOV₃ transfected by WT1 ASODN was decreased.Conclusion The overexpression of WT1 gene might be the biomolecular markers for the clinical diagnosis of ovarian epithelial tumors,especially serous carcinomas.WT1 may play an important role in regulate the proliferation and Apoptosis of ovarian cancer cell lines SKOV₃. WT1 will become a new diagnosis and therapeutic target in ovarian epithelial carcinoma.更多还原