VEGF和PCNA反义寡核苷酸联合治疗裸鼠骨肉瘤的实验研究

The study of VEGF antisense oligonucleotides combination with PCNA antisense oligonucleotides on Osteosarcoma in Nude Mice

目的探讨血管内皮生长因子（VEGF）反义寡核苷酸和增殖细胞核抗原（PCNA）反义寡核苷酸单用或联用对裸鼠骨肉瘤生长的抑制作用。方法制备Balb／c裸鼠皮下骨肉瘤模型24只，随机分为4组：VEGF反义寡核苷酸（ASODN）治疗组、PCNA反义寡核苷酸治疗，组、联合治疗组和对照组，6只／组。接种MG-63人成骨肉瘤细胞后24h内分别用VEGF反义寡核苷酸或（和）PCNA反义寡核苷酸皮下注射进行治疗，对照组只注射生理盐水，2次／周，连续4周；观察各组裸鼠肿瘤的生长情况、裸鼠的一般情况与生存期。断颈处死裸鼠，游标卡尺测量肿瘤体积大小，天平称量肿瘤的重量。结果VEGF-ASODN治疗组、PCNA—ASODN治疗组和联合治疗组裸鼠骨肉瘤的生长均受到不同程度的抑制，抑瘤率分别为44．56％、46．53％和72．71％。结论VEGF和PCNA两种反义寡核苷酸均对骨肉瘤的生长具有抑制作用，两种反义寡核苷酸联合应用比单用的疗效更为显著。

Objective To study the inhibitory effect of VEGF antisense oligonucleotides and/or PCNA antisense oligonucleotides on the growth of Osteosarcoma in Nude Mice. Methods The Osteosarcoma cells were cultured and implanted subcutaneously into 24 nude mice which were subsequently divided into four groups： VEGF ASODN group, PCNA ASODN group, combined group and control group. The different treatment was given respectively at 24 hours alter cell inoculation. The weight and volume of subcutaneous tumors were measured. Result The growth inhibitory rate in VEGF-ASODN group was 44.56%, 46. 53% in the PCNA ASODN group, and 72.71% in the combined group. The combined group which was treated with VEGF-ASODN and PCNA -ASODN showed more effective inhibition than that in the VEGF-ASODN group or the PCNA -ASODN group alone. Conclusion The growth of Osteosarcoma in nude mice can be inhibited by VEGF antisense oligonucleotides and PCNA antisense oligonucleotides respectively. Better inhibitory effect can be obtained by combination use of VEGF-ASODN and PCNA antisense oligonucleotides.