内皮抑素重组腺相关病毒对宫颈癌裸鼠Bcl-2、Bax和Caspase-3蛋白表达的影响  

Effects of Recombinant Adeno-Associated Virus-Endostatin on Expressions of Bcl-2, Bax and Caspase-3 Protein in the Thransplanted Model of Human Cervical Cancer in BALB C Mice

作　　者：荣赟[1] 尹利荣[1] 马洪达[2] 杨维娜[1] 

机构地区：[1]天津医科大学第二医院妇科,300211 [2]天津医科大学第二医院病理科,300211

出　　处：《天津医药》2011年第3期256-259,共4页Tianjin Medical Journal

摘　　要：目的:探讨内皮抑素重组腺相关病毒(rAAV-ES)对人宫颈癌HeLa细胞裸鼠移植瘤的生长抑制作用及其机制。方法:采用左腋皮下接种法,建立人宫颈癌裸鼠模型共60只。造模1周后,随机分为rAAV-ES实验组、空病毒组和磷酸盐缓冲液(PBS)对照组,每组20只。观察裸鼠皮下移植瘤的生长情况,计算肿瘤体积。治疗3周后颈椎脱臼处死裸鼠,完整剥离肿瘤,称瘤质量并计算抑瘤率。HE染色观察肿瘤细胞形态,免疫组织化学技术检测各组肿瘤组织中Bcl-2、Bax和Caspase-3蛋白的表达情况。结果:成功建立宫颈癌裸鼠模型。实验组治疗后肿瘤生长速度较对照组和空病毒组明显减慢(P<0.01),抑瘤率为62.55%。Bcl-2在实验组的阳性率低于空病毒组和PBS对照组(均P<0.01);各组Bax阳性率比较差异无统计学意义(P>0.05);Caspase-3在实验组的阳性率高于空病毒组和PBS对照组(均P<0.01)。Bcl-2与Caspase-3的表达呈负相关(rs=-0.653,P<0.01)。结论:rAAV-ES可抑制宫颈癌移植瘤的生长,其机制可能与通过下调Bcl-2蛋白、激活下游的Caspase-3诱导细胞凋亡有关。Objective： To investigate the inhibition and the mechanism of recombinant adeno-associated virus-endostatin （rAAV-ES） on the growth of human cervical cancer in nude mice. Methods： Sixty mouse models of cervical cancer were established by left anterior subcutaneous inoculation. After 1 week of transplantation, model mice were randomly divided into three groups （twenty in each）, including rAAV-ES group, empty virus group and PBS control group. The weight of nude mice and the tumor size were measured every other day. The tumor volume was calculated. After 3 weeks of treatment, mice were killed by cervical dislocation. The tumor was removed, and tumor volume and weight were measured. The tumor inhibition rate was calculated. HE staining was used to observe the tumor cell morphology. The expressions of Bcl-2, Bax and Caspase-3 in the transplanted tumor were detected by immunohistochemistry. Results： The nude mouse model of cervical cancer was established successfully. Compared with the control group and empty virus group, the tumor growth slowed down significantly in rAAV-ES group（P〈0.01）, and the tumor inhibition rate was 62.55%. Immunohistochemistry showed that the positive rate of Bcl-2 expression was much lower in rAAV-ES group than that of the other two groups （P〈0.01）. There was no significant difference in positive rate of Bax expression between the three groups（P 〉0.05）. The positive rate of Caspase-3 expression was much higher in rAAV-ES group than that of the other two groups （P〈0.01）. The expression of Bcl-2 was negatively correlated with that of Caspase-3（rs =-0.653,P〈0.01）. Conclusion： rAAV-ES inhibited tumor’s growth,and the mechanism may be related to the down-regulating Bcl-2 protein and activating the downstream Caspase-3 to induce cell apoptosis.

关 键 词：内皮抑素类 基因 BCL-2 BCL-2相关X蛋白质 半胱氨酸天冬氨酸蛋白酶3 宫颈肿瘤 疾病模型 动物 小鼠 近交BALB C 

分 类 号：R811[医药卫生—放射医学]