天津医药

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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

荣赟1,尹利荣2,马洪达1,杨维娜1   

  1. 1. 天津医科大学第二医院
    2. 天津医科大学第二医院妇科
  • 收稿日期:2010-05-10 修回日期:2010-11-15 出版日期:2011-03-15 发布日期:2011-03-15
  • 通讯作者: 尹利荣

The effects of endostatin on Expressions of Bcl-2, Bax and Caspase-3 Protein in the thransplanted model of human cervical cancer in BALB/C Mice

  • Received:2010-05-10 Revised:2010-11-15 Published:2011-03-15 Online:2011-03-15

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摘要： 【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，随机分为三组：磷酸盐缓冲液（PBS）对照组，空病毒组和rAAV-ES组，每组20只。隔日观察并记录各组裸鼠皮下移植瘤的生长情况，计算肿瘤体积，绘制肿瘤生长曲线。治疗3周后颈椎脱臼处死裸鼠，完整剥离肿瘤，称瘤重并计算抑瘤率。HE染色观察肿瘤细胞形态，应用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。rAAV-ES组治疗后肿瘤生长速度较对照组和空病毒组明显减慢（P<0.05）,抑瘤率为62.55％。免疫组化结果显示Bcl-2在rAAV-ES组的阳性率（35％）显著低于PBS对照组(80％)和空病毒组(85％)(均P﹤0.01)；Bax在rAAV-ES组的阳性率与其他两组比较无明显改变（均P>0.05），而Bcl-2/Bax比值减低；Caspase-3在rAAV-ES组的阳性率（70％）显著高于PBS组(20％)和空病毒组(25％)(均P﹤0.01)； Bcl-2与Caspase-3的表达呈负相关（r=-0.653，P<0.01）。结论：rAAV-ES可能通过下调 Bcl-2蛋白，降低Bcl-2/Bax比值，激活下游的Caspase-3来诱导细胞凋亡，从而抑制肿瘤生长。

关键词: 内皮抑素, Bcl-2, Bax, Caspase-3, 宫颈癌

Abstract: 【Abstract】Objective:To investigate the inhibition and the mechanism of endostatin on the growth of human cervical cancer in nude mice. Methods: Thirty mice of cervical cancer model were established by left anterior subcutaneous inoculation.After 1 week of transplantation,model mice were randomly divided into three groups ( twenty in each) including PBS control group, Empty virus group and rAAV-ES group . The weight of nude mice and tumor size were measured every other day. Calculate the tumor volume and draw tumor growth curve, After 3 weeks of treatment, mice were killed by cervical dislocation,the tumor was removed and the volume and weight of tumor were measured. The tumor inhibition rate was calculated.HE staining was used to observe the tumor cells morphology.The expressions of Bcl-2、Bax and Caspase-3 in the transplanted tumor were detected by immunohistochemistry. Results:Nude Mice model of cervical cancer were established successfully. Compared with the control group and Empty virus group, the tumor growth slow down significantly in rAAV-ES group, the tumor inhibition rate was 62.55% . Immunohistochemistry showed,the positive rate of Bcl-2 expression was 35% in endostatin group，much lower than that in other two groups(80% and 85%，P﹤0.01).The positive rate of Bax expression had no significant change among the three groups.But the Bcl-2/Bax ratio was lower.The positive rate of Caspase-3 expression was 70% in endostatin group，much higher than that in other two groups(20% and 25%，P﹤0.01);The expression of Bcl-2 is negatively correlated with that of Caspase-3（r=-0.653，P<0.01）.Conclusions: rAAV-ES may be through down-regulating Bcl-2 protein, lowering Bcl-2/Bax ratio, activating the downstream Caspase-3 to induce cell apoptosis, thus inhibit tumor growth.

Key words: endostatin, Bcl-2, Bax, Caspase-3, cervical cancer