探讨硫代修饰脂质体包裹的反义VEGF寡核苷酸对肺癌血流的抑制作用。方法:40只C57BL／6小鼠右腋皮下接种Lewis肺癌细胞后,随机分为4组:VEGF反义寡核苷酸组(ASODN)、VEGF正义寡核苷酸组(SODN)、VEGF错义寡核苷酸组(MODN)及对照组。接种24 h内。4组小鼠分别皮下注射经脂质体包裹的ASODN、SODN及MODN进行治疗,对照组只注射脂质体,每周2次,连续4周。观察各组小鼠肿瘤的生长情况,超声检测肿瘤血管的收缩期峰值速度(PS)及阻力指数(RI),原位杂交法及RT-PCR法对肿瘤内VEGF mRNA表达水平进行检测。结果:ASODN组小鼠肿瘤生长受到显著抑制,PS、RI与其它各组相比有明显差异(P<0．01),VEGF mRNA表达水平亦有明显降低。结论:硫代反义VEGF寡核苷酸能明显抑制肺癌血流,从而抑制肿瘤生长。

investigate whether phosphorothioate-modified antisense vascular endothelial growth factor oligodeoxynucleotides ( VEGF-ASODN) formulated in cationic liposome can inhibit the blood flow of lung cancer. Methods: Lewis lung tumor models were established by subcutaneous injection of Lewis lung carcinoma cells into the right flank of 40 C57BL/6 mice. Twenty-four hours later, mice were randomly assigned into 4 groups; pure liposome, liposome containing ASODN, SODN and MODN. Mice in each group were treated twice a week for 4 weeks. Tumor growth were determined. Peak systolic flow velocity (PS) and resistance index (RI) were measured with a sonographic scanner. Expression of VEGF mRNA were detected by hybridization in situ and RT-PCR. Results: ASODN significantly suppressed the growth of subcutaneous tumors. PS and RI in VEGF-ASODN group were significantly different from those in other 3 groups ( P < 0. 01 ). ASODN markedly downregulated the expression of VEGF at level of mRNA. Conclusion:It is demonstrated that the phosphorothioate-modified ASODN can significantly suppress the growth of tumor by damaging the blood flow of lung cancer.

黑龙江省自然科学基金项目（No.D0346）