OBJECTIVETo investigate the effect of antisense vascular endothelial growth factor (VEGF)(121) cDNA transfection on the growth of K562 cells in nude mice.

METHODSK562 cells transfected with the antisense (AS) or sense (S) VEGF(121) cDNA, and the vector (V, pcDNA3) alone were transplanted subcutaneously into nude mice and the growth of the transfected cells in vivo was investigated. The effects of transfected K562 cells on human bone marrow endothelial cells (BMEC) were analyzed by MTT assay, the microvessel density (MVD) in tumor mass by vWF immunohistochemistry stain.

RESULTSK562/V tumor grew more slowly [(207.5 +/- 192.9) mm(3) vs (445.0 +/- 150.9) mm(3), P < 0.05] and K562/S tumor more rapidly than K562/V tumor did [(1 174.6 +/- 508.7)/mm(3) vs (445.0 +/- 150.9) mm(3), P < 0.01]. K562/S cell culture supernatant was more strongly in promoting the proliferation of BMEC than K562/V supernatant did, but K562/AS supernatant resulted in a marked decrease of the promoting effect as compared with K562/V's. The MVDs in K562/AS, K562/S, and K562/V tumors were [(11.0 +/- 7.6)/0.72 mm(2) vs (50.8 +/- 11.7)/0.72 mm(2) vs (18.9 +/- 7.0)/0.72 mm(2)], respectively.

CONCLUSIONSAntisense VEGF(121) cDNA transfected K562 cells show growth retardation in transplanted nude mice, decrease of tumor MVD, and decrease of promoting BMEC proliferation capacity.

Animals ; Bone Marrow Cells ; cytology ; drug effects ; Cell Division ; genetics ; physiology ; Culture Media, Conditioned ; pharmacology ; DNA, Antisense ; genetics ; DNA, Complementary ; genetics ; Endothelial Growth Factors ; genetics ; physiology ; Endothelium, Vascular ; cytology ; drug effects ; Female ; Humans ; K562 Cells ; Lymphokines ; genetics ; physiology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental ; blood supply ; genetics ; pathology ; Neovascularization, Pathologic ; genetics ; physiopathology ; Transfection ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors