葡萄籽原花青素对卵巢癌裸鼠耐药移植瘤的抑制作用观察  

Inhibitory effect of grape seed proanthocyanidin extract on transplanted drug-resistant ovarian cancer in nude mice

作　　者：蒋兴伟[1] 钟玲[1] 池余刚[1] 胡琴琴[1] 徐蕾[1] 

机构地区：[1]重庆医科大学附属第二医院妇产科,重庆400010

出　　处：《解放军医学杂志》2010年第6期699-701,共3页Medical Journal of Chinese People's Liberation Army

基　　金：重庆医科大学科研课题(XBYB2008035)

摘　　要：目的探讨葡萄籽提取物原花青素(GSPE)对人卵巢癌顺铂耐药细胞COC1/DDP裸鼠皮下移植瘤的抑制作用及其机制。方法 30只COC1/DDP裸鼠建立皮下移植瘤模型,随机分为GSPE高浓度组、GSPE低浓度组、对照组(每组10只),分别以200mg/kgGSPE、100mg/kgGSPE及生理盐水灌胃[10ml/(kg·d)]。3周后处死裸鼠,测量各组移植瘤体积,流式细胞术(FCM)分析细胞凋亡率,RT-PCR、Western blotting检测肿瘤细胞Livin和caspase-3的mRNA、蛋白表达情况。结果 GSPE高、低浓度组皮下移植瘤体积(分别为351.23±15.52、432.51±18.36mm3)明显小于对照组(594.49±16.33mm3,P<0.05)。FCM检测显示GSPE高、低浓度组肿瘤细胞凋亡率分别为66.25%、29.31%,明显高于对照组(1.03%,P<0.01)。与对照组相比,GSPE能明显降低Livin的mRNA、蛋白表达水平(P<0.01或P<0.05),增加caspase-3的mRNA、蛋白表达水平(P<0.01或P<0.05)。结论 GSPE可能是通过降低Livin的表达、增强caspase-3的表达而显著抑制COC1/DDP细胞移植瘤的生长,促进COC1/DDP细胞的凋亡。Objective To study the inhibitory effect of grape seed proanthocyanidin extract （GSPE） on human ovary cancer cis-DDP-resistant cell line COC1/DDP and its underlying mechanism in nude mice. Methods COC1/DDP was subcutaneously transplanted into 30 nude mice successfully. These mice were divided into 3 groups （10 each）：GSPE high dose group （200mg/kg,group H）,GSPE low dose group （100mg/kg,group L） and control group. 10ml/（kg·d） of GSPE solution in respective concentration was given to the mice in group H and group L by gavage,and corresponding volume of 0.9% sodium chloride was given to the mice in control group by the same route. All nude mice were sacrificed 3 weeks after treatment,tumor volume was measured,apoptosis of tumor cells was detected by flow cytometry （FCM）,mRNA and protein expressions of Livin and caspase-3 were assayed by RT-PCR and Western blotting. Results Tumor volumes were significantly smaller in GSPE H group （351.23±15.52mm3） and L group （432.51±18.36mm3） than in control group （594.49±16.33mm3,P0.05）; apoptotic rate of tumor cells were significantly higher in GSPE H group （66.25%） and L group （29.31%） than in control group （1.03%,P0.01）. Compared with control group,mRNA and protein expressions of Livin were significantly lower,but caspase-3 were significantly higher in group H and group L （P0.01 or P0.05）. Conlusions GSPE can inhibit the growth of ovarian cancer COC1/DDP by inducing apoptosis of tumor cells in vivo. Decreased expression of Livin and increased expression of caspase-3 may be mechanism.

关 键 词：花青苷类 卵巢肿瘤 LIVIN 半胱氨酸天冬氨酸蛋白酶3 

分 类 号：R737.31[医药卫生—肿瘤] R979.1[医药卫生—临床医学]