Ad-aVEGF165基因在裸鼠体内对人皮肤恶性黑色素瘤的影响

目的 探讨Ad-aVEGF165基因转染对裸鼠体内人恶性黑色素瘤生长的影响。方法 裸鼠皮下接种人恶性黑色素瘤细胞（A375），1周后瘤块形成并转种和分组干预。随机分为PBS组、Ad-GFP组、Ad-aVEGF组，进行大体观察和组织形态学观察，检测Ad-aVEGF165基因的表达、微血管密度、凋亡指标的变化。结果 成功地建立了裸鼠荷瘤模型；Ad-aVEGF165能抑制体内肿瘤的生长，没有观察到明显的毒副作用；组织学切片能观察GFP基因的表达。Ad-aVEGF组有较多的组织坏死，但其对A375，细胞的凋亡没有明显的影响。Ad-aVEGF165能够抑制A375细胞VEGF的表达，并导致肿瘤的MVD明显减少。结论 Ad-aVEGF165干预人恶性黑色素瘤是可行的，其机理是通过局部缺血而不是通过凋亡起作用的。

The influence of Ad-AVEGF165 on human malignant melanoma growth in nude mice

Objective To investigate the effect of antisense VEGF_ 165 infection on the growth of A_ 375 cells in nude mice. Methods A_ 375 cells were injected s.c into the axilla of the nude mouse. After the tumor formed,we cut it into 16 pieces equally, then transplanted into another 15 nude mice. There were three groups: Group PBS, Group Ad-GFP, and Group Ad-aVEGF. Four weeks after interfere, the mice were sacrificed and their tumors were excised for naked eye and histological observation. The VEGF expression was checked with ISH and immunohistochemistral staining. The micro-vessel density (MVD) in tumor mass was counted by VIII factor immunohistochemistry staining. Results The visible and palpable nodules had developed at all the injected sites. Tumor growth speed was more slowly in Group Ad-aVEGF than that in other groups. GFP gene could express effectively in tumor mass. Ad-aVEGF infection could suppress the growth of tumors,and there were no obvious side effects. Ad-aVEGF resulted more tissue necrosis,but it had no obvious effect on cell apoptosis.VEGF expression was inhibited significantly in Group Ad-aVEGF,and MVD was decreased accordingly. Conclusions Ad-aVEGF interfere may be a new method against human malignant melanoma, whose main mechanism is to induce ischemia, but not apoptosis.