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

Inhibitory effect of 4-HPR combined with DDP on xenografted ovarian carcinoma in nude mice and its relationship with VEGF and u-PA expression

目的:探讨羟苯基维胺脂(N-4-hydroxyphenyl retinode,4-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 endothelial growth factor,VEGF)、尿激酶型纤溶酶原激活物(urokinase type plasminogen activator,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-HPR组、4-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-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-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。

Objective：To explore the inhibitory effect of N4-hydroxyphenyl retinode （4-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 SKOV3 ovarian carcinoma cells were inoculated into BALB/c nude mice. The tumor-bearing nude mice were randomly divided into four groups： control group, DDP group, 4-HPR group, and 4-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 Western blotting, respectively. Results：4-HPR combined with DDP significantly inhibited the growth of xenografted ovarian carcinoma and down-regulated the mRNA and protein expressions of VEGF and u-PA. The inhibitory effect of combination therapy was superior to those treated with 4-HPR and DDP alone. Conclusion ：4-HPR plus DDP significantly inhibited the proliferation of xenografted ovarian carcinoma in nude mice. The effect was associated with the expressions of VEGF and u-PA.