4-HPR联合顺铂对卵巢癌裸鼠移植瘤的抑制作用及其与VEGF、u-PA表达变化的关系.pdfVIP

肿瘤2008年4月第28卷第4期 Tumor Vo1．28，No．4，April，2008 ·305· DOI：10．3781／j．issn．1000-7431．2008．04．008 B~c Research：基础碍 究 4-HPR联合顺铂对卵巢癌裸鼠移植瘤的抑制作用及其与VEGF、u-PA 表达变化的关系 李文学，孙 红 (复旦大学附属妇产科医院妇科，上海 20001 1) [摘要] 目的：探讨羟苯基维胺脂(N-4一hydroxyphenyl retinode，4一HPR)联合顺铂(DDP)对卵巢癌裸鼠移植瘤的生长抑制作用 及其与血管内皮生长因子(vascular endotheliM growth factor，VEGF)、尿激酶型纤溶酶原激活物(urokinase type plasminogen acti— vator，u—PA)表达变化的关系。方 法：BALB／c裸鼠皮下接种卵巢癌SKOV3细胞，成瘤后随机分为4组：对照组、DDP组、 4一HPR组、4一HPR+DDP组。观察各组肿瘤生长情况，应用免疫组织化学法观察各组移植瘤VEGF表达的变化，应用RT—PCR 法检测各组移植瘤VEGF、u—PA mRNA表达的变化；应用Western印迹方法检测各组移植瘤VEGF、u—PA蛋白表达的变化。结 果：4一HPR联合DDP能显著抑制移植瘤的生长，并能抑制VEGF、u—PA mRNA及蛋白的表达，两者联合用药作用优于各单独 用药组。结论：4一HPR联合DDP能显著抑制卵巢癌移植瘤的增殖能力，且这种作用与VEGF、u—PA的表达有关。 [关键词] 卵巢肿瘤；异种移植模型抗肿瘤试验；基因表达4一HPR；顺铂 [中图分类号] R737．31；R73—36 1 [文献标志码] A [文章编号] 1000-7431(2008)04-0305-05 Inhibitory effect of 4-HPR combined with DDP on xenografted ovarian carcinoma in nude mice and its relation- ship wiⅡl VEGF and u-PA expression LI Wen—xue，SUN Hong (Hospital of Obestrics and Gynecology，Fudan University，Shanghai 20001 1，China) [ABSTRACT] objective：To explore the inhibitory effect of N4一hydroxyphenyl retinode(4一HPR)used alone or in combination with DDP on xenografted human ovarian carcinoma in nude mice and its relationship with the expression of vascular endothelial growth factor (VEGF)and urokinase type plasminogen activator(u—PA)．Methods：Human SK0V3 ovarian carcinoma cells were inoculated into BALB／c nude mice．，I’he tumor—bearing nude mice were randomly divided into four groups：control group，DDP group，4一HPR group， and 4一HPR plus DDP group．The growth of xenografted tumors was observed every 3 days．The VEGF expression in xenograft tumors was analyzed by immunohistochemical staining．The mRNA and protein expressions of VEGF and u—PA were analyzed by RT—PCR and Wes— tern blotting．respectively．Results：4一HPR combined with DDP significantly inhibited the growth of xenografted ovaria