[Intravenous delivery of cationic liposomes conjugation to recombinant adenoviral vectors containing human endostatin gene inhibits ovarian cancer growth in nude mice].
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.
Wang
Li
L
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Yang
Li
L
Wu
Yong-kang
YK
Zhao
Xia
X
Wei
Yu-quan
YQ
Li
Wen
W
Tian
Qing
Q
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002412:Cations; D049109:Cell Proliferation / Q000187:drug effects; D018284:Cystadenocarcinoma, Serous / Q000628:therapy; D016503:Drug Delivery Systems; D043169:Endostatins / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use; D008081:Liposomes / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use
D002412:Cations; D043169:Endostatins; D008081:Liposomes; D011994:Recombinant Proteins