Inhibition of K562 leukemia angiogenesis and growth by expression of antisense vascular endothelial growth factor (VEGF) sequence.
Vascular endothelial growth factor (VEGF), a major angiogenic factor, plays a key role in the growth of solid tumor. Recently, expression of VEGF and its receptors has been found on leukemic cells as well as on endothelial cells. VEGF may fulfill a fundamental role in promoting tumor angiogenesis and proliferation by stimulating both endothelial cells and leukemic cells. To investigate the role of VEGF in the angiogenesis and growth of leukemic cell, we used an antisense strategy to downregulate VEGF expression in K562 cells, a human erythroleukemia cell line. Expression of antisense-VEGF in K562 cells reduced the secretion of VEGF protein and inhibited cell survival. The proliferation and migration of human umbilical vein endothelial cells were decreased in response to the conditioned medium (CM) from K562 cells expressed antisense-VEGF, compared to CM from K562 cells transfected with vector control. Moreover, subcutaneous injection of nude mice with antisense-VEGF K562 cells inhibited tumor growth with a reduction of the density of microvessels and an increased apoptosis in those tumors, compared to vector control K562 cells. These results suggest that the efficient downregulation of the VEGF production in leukemic cells using antisense-VEGF may constitute a novel strategy of treatment in leukemia.
He
Rui
R
State Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union of Medical College, Tianjin 300020, China.
Liu
Bin
B
Yang
Chen
C
Yang
Ren Chi
RC
Tobelem
Gerard
G
Han
Zhong Chao
ZC
D045744:Cell Line, Tumor; D002470:Cell Survival; D016373:DNA, Antisense; D015536:Down-Regulation; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D009389:Neovascularization, Pathologic; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology
D016373:DNA, Antisense; D042461:Vascular Endothelial Growth Factor A