靶向融合肽TAT-OSBP-MKK6(E)对卵巢癌裸鼠移植瘤的抑制作用  

Inhibition effect of targeting fusion protein TAT-OSBP-MKK6(E) on human ovarian xenograft tumor in nude mice

作　　者：袁金[1] 康佳丽[1] 廖花[1] 钟嘉莉[1] 王小霞[1] 

机构地区：[1]广州市第一人民医院妇产科,广东广州510180

出　　处：《肿瘤》2015年第2期161-167,共7页Tumor

基　　金：广东省自然科学基金资助项目(编号:S2012010009341)~~

摘　　要：目的:探讨靶向融合肽﹛转录反式激活因子(trans-activator of transcription,TAT)-卵巢癌特异性结合肽(ovarian cancer specii c binding peptide,OSBP)-丝裂原活化蛋白激酶激酶6突变体(E)[mitogen-activated protein kinase kinase 6 mutant(E),MKK6(E)]﹜对卵巢癌裸鼠移植瘤的抑制作用及其可能的机制。方法:建立卵巢癌HO8910细胞的裸鼠皮下移植瘤模型,分为实验组[给予TAT-OSBP-MKK6(E)腹腔注射]、阴性对照组(给予TAT-OSBP腹腔注射)和空白对照组(给予0.9%Na Cl溶液腹腔注射),比较3组裸鼠移植瘤的生长速度、体积和裸鼠体质量;TUNEL法、免疫组织化学法和蛋白质印迹法分别检测移植瘤组织中细胞的凋亡情况、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达以及p38蛋白的表达。结果:实验组裸鼠移植瘤的生长速度滞后于阴性对照组和空白对照组(P<0.05),实验组裸鼠移植瘤体积和裸鼠体质量小于阴性对照组和空白对照组(P均<0.05);而阴性对照组与空白对照组之间的差异无统计学意义(P>0.05)。实验组肿瘤细胞的凋亡指数(apoptosis index,AI)高于阴性对照组和空白对照组(P<0.05),实验组肿瘤组织中PCNA的阳性表达率低于阴性对照组和空白对照组,而p38蛋白的表达水平则相反(P均<0.05);阴性对照组与空白对照组的AI、PCNA阳性表达率及p38蛋白的表达水平之间的差异均无统计学意义(P均>0.05)。结论:靶向融合肽TAT-OSBP-MKK6(E)可抑制卵巢癌裸鼠移植瘤的生长和PCNA的表达,其机制可能与促进细胞凋亡有关。Objective： To investigate the inhibition effect of trans-activator of transcription （TAT）-ovarian cancer specific binding peptide （OSBP）- mitogen-activated protein kinase kinase 6 mutant （E） [MKK6（E）] on human ovarian xenograft tumor in nude mice and its possible mechanism. Methods： The subcutaneous xenograft tumor model of human ovarian cancer HO8910 cells in nude mice was established. Then the tumor-bearing nude mice were randomly divided into three groups： treatment group [TAT-OSBP-MKK6（E） was administered intraperitoneally], negative control group （TAT-OSBP was administered intraperitoneally） and the blank control group （the saline was administered intraperitoneally）. The tumor growth, tumor volume and body weight of nude mice of three groups were observed. The apoptosis and the expressions of proliferating cell nuclear antigen （PCNA） and p38 of xenograft tumors were examined by TUNEL method, immunohistochemistry and Western blotting, respectively. Results： As compared with the negative control and the blank control groups, the growth rate of xenograft tumor in the treatment group was decreased significantly （P 〈 0.05）. The volume of xenograft tumor and the body weight of nude mice in the treatment group were decreased significantly as compared with those in the negative control and the blank control groups （both P 〈 0.05）; there was no difference between the negative control and the blank control groups （P 〉 0.05）. The apoptosis index （AI） value in the treatment group was higher than those in the negative control and the blank control groups （P 〈 0.05）. The positive rate of PCNA expression in the treatment group was lower than those in the negative control and the blank control groups, and the expression level of p38 protein was opposite （all P 〈 0.05）. The AI value, the positive rate of PCNA expression and the expression level of p38 protein were not significantly different between the negative control and the blank control groups �

关 键 词：卵巢肿瘤 动物实验 小鼠 裸 细胞凋亡 重组融合蛋白质类 

分 类 号：R737.31[医药卫生—肿瘤]