[Inhibition of tumor growth and metastasis via local administration of recombinant human endostatin adenovirus].
OBJECTIVE
The growth and metastasis of solid tumors are dependent on angiogenesis. Endostatin, the C-terminal proteolytic fragment of collagen XVIII, is a potent endogenous angiogenesis inhibitor. The authors designed a topical antiangiogenic gene therapy with recombinant human endostatin adenovirus (Ad-hEndo) and assessed its effects on the inhibition of angiogenesis in vitro, and tumor growth and metastasis in vivo.


METHODS
Malignant cells (A549) were infected with Ad-hEndo. The expression of recombinant protein and the inhibition of cultured human umbilical vein endothelial were investigated. Immunodeficient A549 nude mice were treated with intratumoral injection of Ad-hEndo, the empty vector Ad-control or saline (NS). The dose-response, side effects, and serum concentration of endostatin were observed.


RESULTS
Recombinant endostatin protein was detected in the infected tumor cells with different MOI Ad-hEndo and its inhibitory effect on endothelial cells growth was shown. In animal study, the volume of tumor and the number of pulmonary metastatic lesions in the Ad-hEndo treatment group were significantly smaller than those in the control groups (P<0.05).


CONCLUSIONS
The present findings provide evidence of the anti-tumor effects of the endostatin and may be important for the further use of it in topical antiangiogenic gene therapy of cancer.
Wu
Yang
Y
Center for Biotherapy of Cancer and Cancer Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041 P. R. China.
Yang
Li
L
Zhao
Xia
X
Su
Jing-mei
JM
Hu
Bing
B
Liu
Ji-yan
JY
Niu
Ting
T
Luo
Yan
Y
Li
Qiu
Q
Wei
Yu-quan
YQ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D043169:Endostatins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D042783:Endothelial Cells; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology; D023041:Xenograft Model Antitumor Assays
D043169:Endostatins; D011994:Recombinant Proteins