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[阳离子脂质体与含人内皮抑素基因的重组腺病毒载体偶联的静脉内递送抑制裸鼠卵巢癌生长]

[Intravenous delivery of cationic liposomes conjugation to recombinant adenoviral vectors containing human endostatin gene inhibits ovarian cancer growth in nude mice].

作者信息

Wang Li, Yang Li, Wu Yong-kang, Zhao Xia, Wei Yu-quan, Li Wen, Tian Qing

机构信息

Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Mar;40(2):190-4.

Abstract

OBJECTIVE

To evaluate the anticancer effect of liposome plus Ad-Endostatin complex on human ovarian serous cystocarcinoma.

METHODS

The recombinant endostatin was expressed in the SKOV3 cells transfected with constructed adenovirus. The nude mice models with human ovarian serous cystocarcinoma were divided into six groups randomly: (1) Ad-hEndo-H plus liposome group (abbreviation: lipo+Ad-hEndo-H), i.v. administration of 1 x 10(9) pfu (plaque-forming units) recombinant adenovirus plus 200 microg liposome (n=5); (2) Ad-hEndo-L plus liposome group (abbreviation: lipo+Ad-hEndo-L), i.v. administration of 1 x 10(8) pfu recombinant adenovirus plus 20 microg liposome (n=5); (3) Ad-hEndo group, i.v. administration of 1 x 10(9) pfu recombinant adenovirus (n=4) (4) Ad-null plus liposome group, i.v. administration of 1 x 10(9) pfu adenovirus plus 200 microg liposome (n=4); (5) liposome group, i.v. administration of liposome 200 microg (n=4) (6) NS group, i.v. administration of equal volume of normal saline as above (n=4). The tumor size was monitored every 7 days. All of the nude mice were sacrificed 49 days after the tumor establishment. The tumors were removed and weighted. The micro-vessel density (MVD) was counted and the apoptotic cells were measured in the tumors tissue by TUNEL. The effect of the antibody of adenovirus was investigated with the SKOV3 cells transfected with liposome-complexed adenovirus.

RESULTS

The tumors of the mice in the lipo+Ad-hEndo-H and lipo+Ad-hEndo-L groups weighted 54.74% and 70.65% lighter than the NS controls, respectively (P < 0.05). The tumors in the lipo+Ad-hEndo-L and lipo+Ad-hEndo-H groups had fewer MVD and more apoptotic cells than those in the other groups (P < 0.05). The antibody of adenovirus had less impact on the adenovirus capability of transfect when it was combined with liposome than without liposome.

CONCLUSIONS

The liposome plus Ad-Endostatin complex inhibits the growth of human ovarian serous cystocarcinoma effectively. Lower dose of repeated injection of adenovirus with liposome is preferable.

摘要

目的

评估脂质体加Ad - 内皮抑素复合物对人卵巢浆液性囊腺癌的抗癌作用。

方法

重组内皮抑素在转染构建好的腺病毒的SKOV3细胞中表达。将人卵巢浆液性囊腺癌裸鼠模型随机分为六组:(1)Ad - hEndo - H加脂质体组(简称:脂质体+Ad - hEndo - H),静脉注射1×10⁹ 空斑形成单位(pfu)重组腺病毒加200μg脂质体(n = 5);(2)Ad - hEndo - L加脂质体组(简称:脂质体+Ad - hEndo - L),静脉注射1×10⁸ pfu重组腺病毒加20μg脂质体(n = 5);(3)Ad - hEndo组,静脉注射1×10⁹ pfu重组腺病毒(n = 4);(4)Ad - 空载体加脂质体组,静脉注射1×10⁹ pfu腺病毒加200μg脂质体(n = 4);(5)脂质体组,静脉注射200μg脂质体(n = 4);(6)生理盐水组,静脉注射与上述等量的生理盐水(n = )。每7天监测肿瘤大小。所有裸鼠在肿瘤接种后49天处死。取出肿瘤并称重。计数微血管密度(MVD),并通过TUNEL法检测肿瘤组织中的凋亡细胞。用脂质体复合腺病毒转染的SKOV3细胞研究腺病毒抗体的作用。

结果

脂质体+Ad - hEndo - H组和脂质体+Ad - hEndo - L组小鼠的肿瘤重量分别比生理盐水对照组轻54.74%和70.65%(P < 0.05)。脂质体+Ad - hEndo - L组和脂质体+Ad - hEndo - H组肿瘤的MVD比其他组少,凋亡细胞比其他组多(P < 0.05)。腺病毒抗体与脂质体联合时对腺病毒转染能力的影响比不与脂质体联合时小。

结论

脂质体加Ad - 内皮抑素复合物能有效抑制人卵巢浆液性囊腺癌的生长。较低剂量的腺病毒与脂质体重复注射更可取。

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