Increased suppression of oncolytic adenovirus carrying mutant k5 on colorectal tumor.
Angiogenesis plays a key role in the development of a wide variety of malignant tumors. The approach of targeting antiangiogenesis has become an important field of cancer gene therapy. In this study, the antiangiogenesis protein K5 (the kringle 5 of human plasminogen) has been mutated by changing leucine71 to arginine to form mK5. Then the ZD55-mK5, which is an oncolytic adenovirus expressing mK5, was constructed. It showed stronger inhibition on proliferation of human umbilical vein endothelial cell. Moreover, in tube formation and embryonic chorioallantoic membrane assay, ZD55-mK5 exhibited more effective antiangiogenesis than ZD55-K5. In addition, ZD55-mK5 generated obvious suppression on the growth of colorectal tumor xenografts and prolonged the life span of nude mice. These results indicate that ZD55-mK5 is a potent agent for inhibiting the tumor angiogenesis and tumor growth.
Fan
Jun Kai
JK
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xiao
Tian
T
Gu
Jin Fa
JF
Wei
Na
N
He
Ling Feng
LF
Ding
Miao
M
Liu
Xin Yuan
XY
D000256:Adenoviridae; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000098:blood supply*; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses; D010446:Peptide Fragments / Q000235:genetics*; D010958:Plasminogen / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D010446:Peptide Fragments; C491499:plasminogen kringle 5; D010958:Plasminogen