Intramuscular electroporation of a plasmid encoding human plasminogen kringle 5 induces growth inhibition of Lewis lung carcinoma in mice.
Tumor growth and metastasis depend critically on blood vessel formation. Antiangiogenesis, therefore, represents a promising strategy for cancer therapy. The kringle 5 (K5) domain of human plasminogen is a potent angiogenesis inhibitor. To investigate whether intramuscular electroporation (EP) of K5 has antitumor activity in mouse tumor models, we constructed a plasmid encoding K5 (pVAX1-K5). Hela cells transfected with this plasmid produced and secreted K5 that inhibited the migration of human microvascular endothelial cells. Intramuscular EP treatment of pVAX1-K5 inhibited the growth of Lewis lung carcinoma and prolonged the survival time of tumor-bearing mice. Angiogenesis was obviously inhibited, and apoptosis was induced in tumor cells of mice that received intramuscular EP of pVAX1-K5. On the contrary, intramuscular injection of pVAX1-K5 without EP failed to show the same effects. The data indicate that intramuscular EP of plasmid DNA encoding the K5 domain is an effective strategy for the experimental treatment of cancer by expressing K5.
Li
Yonghong
Y
Biotechnology Center of the Forth Military Medical University, Xi'an, People's Republic of China.
Han
Wei
W
Zhang
Yongchao
Y
Yuan
Liyong
L
Shi
Xinchang
X
Yu
Yongli
Y
Zhang
Yingqi
Y
Wang
Junzhi
J
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000628:therapy*; D018274:Electroporation / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology; D015316:Genetic Therapy / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism*; D010958:Plasminogen / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary
D020533:Angiogenesis Inhibitors; D010446:Peptide Fragments; C491499:plasminogen kringle 5; D010958:Plasminogen