携带人内皮抑素基因的肿瘤特异性增殖型腺病毒对卵巢癌的体内治疗作用

目的:探讨携带人内皮抑素基因的肿瘤特异性增殖型腺病毒CX-hE对卵巢癌裸鼠瘤株OV-90的抑制作用.方法:BALB/c裸鼠右背部皮下接种OV-90细胞成瘤.(1)18只荷瘤裸鼠随机分为PBS对照组、CX-hE治疗组和Ad-hE治疗组,皮下种植瘤内直接注射.各药物隔日注射1次,共注射5次.取肝脏组织行常规病理检查.(2)另15只荷瘤裸鼠随机分3组,分别瘤内单次注射CX-hE、Ad-hE和ONYX-015病毒纯化液.注射后第1、3、7天球后静脉取血ELISA检测人内皮抑素浓度,肿瘤组织行Hexon单克隆抗体免疫组化染色及微血管免疫组化染色.结果:(1)CX-hE组肿瘤生长速度较缓慢,开始治疗后2周肿瘤体积已明显小于Ad-hE组(P＜0.05)和PBS组(P＜0.01).常规H-E染色显示CX-hE组肿瘤组织内见散在坏死灶;肝脏无明显病理变化.(2)瘤内单次注射各药物后,裸鼠血清中均可检测到内皮抑素蛋白表达,随时间延长表达量逐渐升高.CX-hE组人内皮抑素浓度始终高于Ad-hE组(P＜0.01),增长速度较快.CX-hE单次瘤内注射2周,肿瘤Hexon免疫组化染色可见大量密集分布的阳性肿瘤细胞.CX-hE组肿瘤微血管免疫组化可见残余的癌巢内尚有散在分布的阳性血管内皮细胞.结论:瘤内直接注射的治疗方法可使瘤生长速度减慢,CX-hE治疗效果优于Ad-hE,未观察到各治疗组肿瘤生长停止或完全消退的理想治疗效果.

Therapeutic effects of tumor-selective replication-competent adenovirus carrying human endostatin gene on ovarian cancer:an in vivo study in mice

Objective:To study the inhibitory effect of tumor-selective replication-competent adenovirus-mediated human endostatin(CX-hE)on transplanted ovarian cancer(OV-90) in nude mice.Methods: BALB/c nude mice were inoculated subcutaneously with OV-90 cells to establish the animal model bearing human ovarian cancer.Eighteen nude mice bearing cancer were divided into 3 groups to receive intratumoral injection of PBS,CX-hE or Ad-hE,1/2 d,5 times.Then their livers were harvested for pathologic examination.Another 15 nude mice were divided into 3 groups to receive single intratumoral injection of CX-hE,Ad-hE or ONYX-015.Venous blood was collected on day 1,3 and 7 after injection for hEndo measurement by ELISA.The tumors were harvested for pathologic examination and immunohistochemical staining.Results: The tumors grew more slowly in CX-hE group and their sizes were markedly smaller than those of Ad-hE group(P<0.05) and PBS group(P<0.01).Endostatin levels were detected in the sera of nude mice in all single injection groups,and the endostatin expression in CX-hE group increased as time passing by.The endostatin level in CX-hE treated group was much higher(P<0.01) and increased faster than that in Ad-hE treated group.Immunohistochemical staining for Hexon of adenovirus capsid showed more positive tumor cells in the tumor tissues treated with CX-hE.Immunohistochemical staining for vWF revealed a decreased microvessel density in the tumor tissues treated with CX-hE.Conclusion: CX-hE and Ad-hE can inhibit tumor growth and the effect of CXhE is superior to that of Ad-hE.There is no growth halt or disappearance of tumors in all groups.