转染反义VEGF cDNA抑制K562细胞裸鼠体内生长和肿瘤内血管生成  

Inhibition of K562 cell growth and tumor angiogenesis in nude mice by antisense VEGF_(121) cDNA transfection

作　　者：阮国瑞[1] 刘艳荣[1] 陈珊珊[1] 秦亚溱[1] 李金兰[1] 付家瑜[1] 于弘[1] 常艳[1] 

机构地区：[1]北京大学人民医院,血液病研究所,100044

出　　处：《中华血液学杂志》2002年第4期179-182,共4页Chinese Journal of Hematology

基　　金：国家自然科学基金资助项目 ( 39970 314)

摘　　要：目的　探讨转染反义血管内皮细胞生长因子 (VEGF)cDNA对慢性髓系白血病 (CML)急变细胞株K5 6 2裸鼠体内生长的影响。方法　利用转染反义 (AS)、正义 (S)VEGF1 2 1 cDNA及空载体 (V ,pcDNA3质粒 )的K5 6 2细胞株 ,观察转染细胞在裸鼠体内成瘤及生长情况 ;免疫组化法比较其裸鼠移植瘤微血管密度 (MVD) ;MTT法观察其对骨髓内皮细胞体外增殖的影响。结果　转染反义VEGF1 2 1 cDNA的K5 6 2 AS细胞组的瘤块体积小、生长慢于K5 6 2 V组 [(2 0 7.5± 192 .9)mm3 vs (4 45 .0± 15 0 .9)mm3 ,P <0 0 5 ],而K5 6 2 S组瘤块体积大于K5 6 2 V组 [(1174.6± 5 0 8.7)mm3 vs (4 45 .0± 15 0 .9)mm3 ,P <0 .0 1]。K5 6 2 AS组裸鼠体内肿瘤MVD低于K5 6 2 V组 [(11.0± 7.6 ) 0 .72mm2 vs (18.9± 7.0 ) 0 .72mm2 ,P <0 0 5 ],而K5 6 2 S组则高于K5 6 2 V组 [(5 0 .8± 11.7) 0 .72mm2 vs (18.9± 7.0 ) 0 .72mm2 ,P <0 .0 1]。K5 6 2 AS细胞的培养上清刺激骨髓内皮细胞增殖能力弱于K5 6 2 V ,而K5 6 2 S细胞的结果相反。结论　转染反义VEGF1 2 1 cDNA抑制K5 6 2细胞裸鼠体内肿瘤生长 ,降低裸鼠瘤块内MVD 。Objective To investigate the effect of antisense vascular endothelial growth factor (VEGF) 121 cDNA transfection on the growth of K562 cells in nude mice. Methods K562 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. Results K562/V tumor grew more slowly [(207.5±192.9)mm 3 [WTBX]vs (445.0±150.9)mm 3,P<0.05] and K562/S tumor more rapidly than K562/V tumor did and K562/S tumor more rapidly than K562/V tumor did [(1 174.6±508.7)/mm 3 [WTBX]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 . 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 [WTBX]vs (50.8±11.7)/0.72 mm 2 vs (18.9±7.0)/0.72 mm 2], respectively. , respectively. Conclusions Antisense VEGF 121cDNA transfected K562 cells show growth retardation in transplanted nude mice, decrease of tumor MVD, and decrease of promoting BMEC proliferation capacity.

关 键 词：转染反义VEGF CDNA 血管内皮细胞生长因子 血管生成 慢性髓系白血病 CML 

分 类 号：R730.2[医药卫生—肿瘤]