血管抑素基因转染联合化疗药物对人卵巢癌裸鼠腹腔移植瘤的治疗作用

Treatment of Intraperitoneal Implanted Human Ovarian Carcinoma of Nude Mice by Angiostatin Gene and Chemotherapy In Vivo

目的研究血管抑素(angiostatin)基因转染联合化疗药物顺铂对人卵巢癌裸鼠腹腔移植瘤的协同治疗作用及其相关机制。方法使用人卵巢癌细胞株SKOV3建立人卵巢癌裸鼠腹腔移植瘤模型。将荷瘤裸鼠随机分为4组,分别注射空质粒PcDNA3、angiostatin/PcDNA3、化疗药物顺铂、angiostatin/PcDNA3+顺铂,质粒用脂质体DOTAP介导转染细胞。观察各组动物的腹水量及腹腔荷瘤量,检测各组肿瘤组织中angiostatin的表达和微血管密度,利用TUNEL染色法行原位细胞凋亡分析。结果联合治疗组裸鼠的腹水量(P<0.01)及腹腔瘤负荷(P<0.005)均显著低于其他实验组;肿瘤组织中angiostatin蛋白局部高表达,微血管密度显著低于其他实验组(P<0.01),细胞凋亡指数显著高于其他实验组(P<0.05)。结论Angiostatin基因联合化疗治疗人卵巢癌裸鼠腹腔移植瘤可以产生协同抑制作用,多途径联合用药是提高疗效的有效方法之一。

Objective To observe the effects of angiostatin gene combined with chemotherapy on implanted human ovarian carcinoma of nude mouse. Methods The mice were randomly divided into four groups after 7 days of the intraperitoneal injection of tumor cells （4 ± 106 ） , and injected respectively with empty plasmid pcDNA3.0, angiostatin plasmid, cisplatin, and angiostatin plasmid ± cisplatin. For combinational treatment, reagents were delivered in a timed fashion, where angiostatin plasmid was injected first, followed by cisplatin 24h later. The tumor samples were prepared to be used in the examinations of the expression of angiostatin with immunohistochemistry, of MVD in the tumor with immunohistochemistry, and of cell apoptosis with TUNEL staining. Results Tumor growth and ascites formation were inhibited in all 3 groups except for the control group. The therapeutic effectiveness in the combined group was more significant than in the other two groups. In this group, MVD （32.5 ±4.3） was the lowest and apoptosis index （5.12 ± 0.63） was the highest （P 〈 0.01 ） . Conclusions Angiostatin gene therapy combined with chemotherapy has a synergistic effect on the inhibition of ovarian cancer angiogenesis and ascites formation. Combining multiple therapies to treat ovarian cancer is an effective strategy.